Chemokine peptide cocktails and methods of use

Abstract

Methods for treating or inhibiting fibrosis in a subject by administering specific chemokine cocktails are described. The chemokine cocktails include combinations of CXCL4, CXCL9, CXCL10, CXCL11 and / or CXCL12 proteins, or the combination of CXCL1 and CXCL8 proteins. Methods for increasing extracellular matrix (ECM) production and / or treating a wound in a subject by administering specific chemokine cocktails are also described. In these methods, the cocktails include CXCL1 and CXCL8 proteins and optionally further include a CCL2 protein.

Description

[0001]8123-112369-02 05552CHEMOKINE PEPTIDE COCKTAILS AND METHODS OF USE CROSS REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No.63 / 669,191, filed July 9, 2024, which is herein incorporated by reference in its entirety. FIELD This disclosure concerns chemokine protein cocktails and their use to modulate fibrosis, treat wounds and / or enhance extracellular matrix (ECM) production. ACKNOWLEDGMENT OF GOVERNMENT SUPPORT This invention was made with government support under AR068317 awarded by the National Institutes of Health. The government has certain rights in the invention. INCORPORATION OF ELECTRONIC SEQUENCE LISTING The electronic sequence listing, submitted herewith as an XML file named 8123-112369- 02.xml (18,897 bytes), created on June 30, 2025, is herein incorporated by reference in its entirety. BACKGROUND Organ fibrosis is a common pathological feature of multiple disorders. It is estimated to cause 45% of deaths in developed countries. Fibrotic diseases can impact single organs or involve multiple organs, such as in systemic sclerosis (scleroderma, SSc). Chronic inflammation and excessive accumulation of ECM, such as in collagen and fibronectin, alter tissue structure and limit biomechanical function. Fibroblast production of ECM and tissue remodeling factors are directed by autocrine and paracrine signals, coming from chemokines and cytokines. A need remains for improved treatments for fibrosis. SUMMARY Described herein are chemokine cocktails containing specific combinations of chemokine proteins for treating or inhibiting fibrosis, increasing extracellular matrix (ECM) production, and / or treating wounds in a subject. Provided herein are methods of treating or inhibiting fibrosis in a subject. In some aspects, the method includes administering to the subject an effective amount of a chemokine cocktail that includes two or more of a CXCL4 protein, a CXCL9 protein, a CXCL10 protein, and a CXCL11 protein, or biologically active fragments or variants thereof; two or more of a CXCL4 protein, a CXCL9 protein, a CXCL10 protein, a CXCL11 protein and a CXCL12 protein, or biologically active8123-112369-02 05552fragments or variants thereof; or a CXCL1 protein and a CXCL8 protein, or biologically active fragments or variants thereof. In some examples, the chemokine proteins are human proteins. In some examples, the fibrosis is fibrosis of the skin, lung, heart, kidney or liver. Also provided herein are methods for increasing ECM production and / or treating a wound in a subject. In some aspects, the method includes administering to the subject an effective amount of a chemokine cocktail that includes a CXCL1 protein and a CXCL8 protein, or biologically active fragments or variants thereof; or a CXCL1 protein, a CXCL8 protein, and a CCL2 protein, or biologically active fragments or variants thereof. In some examples, the chemokine proteins are human proteins. In some aspects of the disclosed methods, the chemokine cocktail is formulated for topical, intranasal, inhalation, intravenous, intramuscular, intradermal, or subcutaneous administration. The foregoing and other objects, features, and advantages of the invention will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1: ELR- chemokines and chemokine cocktails do not significantly alter fibroblast transcription of matrix molecules. Fibroblasts were treated for 24 hours with CXCL4, CXCL9, CXCL10, CXCL11, or CXCL12 individually, or with chemokine Cocktail 1 (C1: CXCL4, CXCL9, CXCL10 and CXCL11) or chemokine Cocktail 2 (C2: CXCL4, CXCL9, CXCL10, CXCL11 and CXCL12). mRNA levels of tenascin C (TNC), collagen type 1 alpha 1 (COL1A1), decorin (DCN), actin alpha 2 (ACTA2), and fibronectin 1 (FN1) were quantified by RT-qPCR, expressed as mean ± SD relative to glyceraldehyde-3-phosphatge dehydrogenase (GAPDH), and normalized to the untreated control. Significance was evaluated by one-way ANOVA and the Dunnett’s post hoc comparison test, * = p < 0.05. NS, not significant. FIG.2: ELR+ chemokines and chemokine cocktails, particularly CXCL8, decrease fibroblast transcription of matrix molecules. Fibroblasts were treated for 24 hours with CXCL1, CXCL8, or CCL2 individually, or with chemokine Cocktail 3 (C3: CXCL1, CXCL8, and CCL2) or chemokine Cocktail 4 (C4: CXCL1 and CXCL8). mRNA levels of TNC, COL1A1, DCN, ACTA2, and FN1 were quantified by RT-qPCR, expressed as mean ± SD relative to GAPDH, and normalized to the untreated control. Significance was evaluated by one-way ANOVA and the Dunnett’s post hoc comparison test, * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001. NS, not significant. FIG.3: ELR- chemokines and chemokine cocktails increase ECM gene expression in primary dermal transforming growth factor (TGF)-β-activated fibroblasts. Fibroblasts were stimulated with TGF-β and treated for 24 hours with CXCL4, CXCL9, CXCL10, CXCL11, or CXCL128123-112369-02 05552individually, or with C1 (CXCL4, CXCL9, CXCL10 and CXCL11) or C2 (CXCL4, CXCL9, CXCL10, CXCL11 and CXCL12). mRNA levels of TNC, COL1A1, DCN, ACTA2, and FN1 were quantified by RT-qPCR, expressed as mean ± SD relative to GAPDH, and normalized to the untreated control. Significance was evaluated by one-way ANOVA and the Dunnett’s post hoc comparison test and was compared against untreated control (*) or cells treated with TGF-β alone ($), * / $ = p < 0.05, ** / $$ = p < 0.01, *** / $$$ = p < 0.001, **** / $$$$ = p < 0.0001. NS, not significant. FIG.4: ELR+ chemokines and chemokine cocktails increase ECM gene expression in primary dermal TGF-β-activated fibroblasts. Fibroblasts were treated for 24 hours with TGF-β in combination with CXCL1, CXCL8, or CCL2 individually, or with C3 (CXCL1, CXCL8, and CCL2) or C4 (CXCL1 and CXCL8). mRNA levels of TNC, COL1A1, DCN, ACTA2, and FN1 were quantified by qRT-PCR, expressed as mean ± SD relative to GAPDH, and normalized to the untreated control. Significance was evaluated by one-way ANOVA and the Dunnett’s post hoc comparison test, and was compared against untreated control (*) or cells treated with TGF-β alone ($), * / $ = p < 0.05, ** / $$ = p < 0.01, *** / $$$ = p < 0.001, **** / $$$$ = p < 0.0001. FIGS.5A-5D: CXCL8 consistently with TGF-β cytokine cocktail stimuli in human dermal fibroblasts induces lysyl oxidase (LOX) in TGF-β downstream signaling activity. Human dermal fibroblasts (3000 cells / well) were cultured with (FIGS.5B, 5D) TGF-β or (FIGS.5A, 5C) left unstimulated. After 24 hours, cells were stimulated with CXCL1, CXCL2, or CXCL8 alone or in combination, as indicated, for 24 hours. Cells were then fixed and stained for LOX and counterstained with DAPI (blue). Images were taken at 20X. Fluorescence was measured using Image J software and is displayed as mean ± SD. Significance was evaluated by one-way ANOVA and the Dunnett’s post hoc comparison test, and was compared against untreated control (*) or cells treated with TGF-β alone ($), * / $ = p < 0.05, ** / $$ = p < 0.01, *** / $$$ = p < 0.001, **** / $$$$ = p < 0.0001. FIGS.6A-6D: CXCL8 increases fibroblast production of decorin in a TGF-β-dependent manner. Human dermal fibroblasts (3000 cells / well) were cultured with (FIGS.6B, 6D) TGF-β or (FIGS.6A, 6C) left unstimulated. After 24 hours, cells were stimulated with CXCL1, CXCL2, or CXCL8 alone or in combination, as indicated, for 24 hours. Cells were then fixed and stained for decorin and counterstained with DAPI. Images were taken at 20X. Fluorescence was measured using Image J software and is displayed as mean ± SD. Significance was evaluated by one-way ANOVA and the Dunnett’s post hoc comparison test. Significance was determined against untreated control (*) or cells treated with TGF-β alone ($), * / $ = p < 0.05, ** / $$ = p < 0.01, *** / $$$ = p < 0.001, **** / $$$$ = p < 0.0001. NS, not significant. FIGS.7A-7D: TGF-β enhances ELR+ chemokine upregulation of fibronectin (FN1). Human dermal fibroblasts (3000 cells / well) were cultured with (FIGS.7B, 7D) TGF-β or (FIGS.7A, 7C) left unstimulated. After 24 hours, cells were stimulated with CXCL1, CXCL2, or CXCL8 alone or in combination, as indicated, for 24 hours. Cells were then fixed and stained for fibronectin and8123-112369-02 05552counterstained with DAPI. Images were taken at 20X . Fluorescence was measured using Image J software and is displayed as mean ± SD. Significance was evaluated by one-way ANOVA and the Dunnett’s post hoc comparison test, and was compared against untreated control (*) or cells treated with TGF-β alone ($), * / $ = p < 0.05, ** / $$ = p < 0.01, *** / $$$ = p < 0.001, **** / $$$$ = p < 0.0001. FIGS.8A-8D: CXC ELR+ chemokines upregulate phospho-SMAD (pSMAD) expression with and without TGF-β stimulation. Human dermal fibroblasts (3000 cells / well) were cultured with (FIGS.8B, 8D) TGF-β or (FIGS.8A, 8C) left unstimulated. After 24 hours, cells were stimulated with CXCL1, CXCL2, or CXCL8 alone or in combination, as indicated, for 24 hours. Cells were then fixed and stained for pSMAD2 / 3 and counterstained with DAPI. Images were taken at 20X. Fluorescence was measured using Image J software and is displayed as mean ± SD. Significance was evaluated by one-way ANOVA and the Dunnett’s post hoc comparison test, and was compared against untreated control (*) or cells treated with TGF-β alone ($), * / $ = p < 0.05, ** / $$ = p < 0.01, *** / $$$ = p < 0.001, **** / $$$$ = p < 0.0001. FIGS.9A-9C: RNA sequence analysis of cocktail gene enrichment analysis dependent on TGF-β and ELR+ chemokines. Gene cluster analysis of differential expression genes was performed to evaluate the effect of chemokines in modifying the effects of TGF-β under the different cluster cocktail cytokines. The interactions from different experimental conditions on differential expressed genes were evaluated, particularly on CXCL8 and CXCL1 with and without TGF-β. Through clustering genes in similar expression pattern, unknown functions of transcripts were recognized, with the reason that same kind of transcripts have similar functions or participate in the same metabolic processes or cellular pathways. Hierarchical clustering analysis was carried out with the log10(FPKM+1) of union differential expression genes of all comparison groups under different experimental conditions (FIG.9A). Venn diagrams (FIG.9B) and volcano diagrams visually show the whole distribution of differential expression genes. For the samples with biological replicates, the threshold of differential expression genes is: padj < 0.05. For the samples without biological replicates, the threshold of differential expression genes is: |log2(FoldChange)| > 1 and qvalue < 0.005 (FIG.9C). FIGS.10A-10D: CXCL8 conditional increase in ECM and collagen activity via RNA seq analysis. CXCL8 holds a strong expression of cell-substrate junction and focal adhesion expression interaction analysis when compared to all other groups (FIGS.10A-10B) as well as high interaction resemblance in extracellular matrix organization expression (FIGS.10C-10D). Gene expression interaction and association studies using RNA seq analysis were guided by the previous in vitro and ex vivo results. Differential expression analysis between two groups / conditions were performed using the DESeq2 R package (2_1.6.3). The resulting p-values were adjusted using the Benjamini and Hochberg’s approach for controlling the False Discovery Rate (FDR). Genes with an adjusted p-value < 0.05 found by DESeq2 were assigned as differentially expressed. Gene Ontology (GO) enrichment8123-112369-02 05552analysis of differentially expressed genes was implemented by the cluster Profiler R package, in which gene length bias was corrected. GO terms with corrected p-values less than 0.05 were considered significantly enriched by differentially expressed genes (FIGS.10A-10B) and in reactome data analysis (FIGS.10C-10D). FIG.11: Differential regulation of genes associated with extracellular matrix organization with ELR+ genes individually or in combination. Displayed here are the log2 fold change values for all genes incorporated into the Reactome term: Extracellular Matrix Organization with the most highly enriched Terms found by Reactome enrichment analysis of fibroblasts treated with TGF-β alone or with CXCL1, CXCL8, or CXCL1 + CXCL8 and compared to control. The log2 fold change of each gene and the color represents the treatment group of TGF-β and either CXCL1, CXCL8, or CXCL1 and CXCL8 in tandem. FIG.12: CXCL4, CXCL8, and ELR- chemokine cocktails upregulate ECM FN1 and DCN mRNA expression levels in SSc primary human dermal fibroblasts. Primary human dermal fibroblasts from SSc patients (n = 2 for each group) with a low mRSS (patients 12, 17) or high mRSS (patients 34, 43) were treated with chemokines or chemokine cocktails as indicated. mRNA levels of FN1 and DCN were quantified by qRT-PCR, expressed as mean ± SD relative to GAPDH, and normalized to the untreated control. Significance was evaluated by one-way ANOVA and the Dunnett’s post hoc comparison test between control groups and chemokine / chemokine cocktail-treated groups. Significance is displayed as * = p < 0.05 and ** = p < 0.01. FIG.13: Graphical depiction of the methodology, approach and conclusions of the studies directed to chemokine cocktail stimulation of fibroblasts and subsequent analysis. SEQUENCES The nucleic acid and amino acid sequences listed in the accompanying sequence listing are shown using standard letter abbreviations for nucleotide bases, and single letter code for amino acids, as defined in 37 C.F.R.1.822. Only one strand of each nucleic acid sequence is shown, but the complementary strand is understood as included by any reference to the displayed strand. In the accompanying sequence listing: SEQ ID NO: 1 is the amino acid sequence an exemplary human CXCL1 protein. ASVATELRCQCLQTLQGIHPKNIQSVNVKSPGPHCAQTEVIATLKNGRKACLNPASPIVKKIIE KMLNSDKSN SEQ ID NO: 2 is the amino acid sequence an exemplary human CXCL4 protein. EAEEDGDLQCLCVKTTSQVRPRHITSLEVIKAGPHCPTAQLIATLKNGRKICLDLQAPLYKKII KKLLES SEQ ID NO: 3 is the amino acid sequence an exemplary human CXCL8 protein.8123-112369-02 05552SAKELRCQCIKTYSKPFHPKFIKELRVIESGPHCANTEIIVKLSDGRELCLDPKENWVQRVVEK FLKRAENS SEQ ID NO: 4 is the amino acid sequence an exemplary human CXCL9 protein. TPVVRKGRCSCISTNQGTIHLQSLKDLKQFAPSPSCEKIEIIATLKNGVQTCLNPDSADVKELIK KWEKQVSQKKKQKNGKKHQKKKVLKVRKSQRSRQKKTT SEQ ID NO: 5 is the amino acid sequence an exemplary human CXCL10 protein. VPLSRTVRCTCISISNQPVNPRSLEKLEIIPASQFCPRVEIIATMKKKGEKRCLNPESKAIKNLLK AVSKERSKRSP SEQ ID NO: 6 is the amino acid sequence an exemplary human CXCL11 protein. FPMFKRGRCLCIGPGVKAVKVADIEKASIMYPSNNCDKIEVIITLKENKGQRCLNPKSKQARLI IKKVERKNF SEQ ID NO: 7 is the amino acid sequence an exemplary human CXCL12 protein. KPVSLSYRCPCRFFESHVARANVKHLKILNTPNCALQIVARLKNNNRQVCIDPKLKWIQEYLE KALNKRFKM SEQ ID NO: 8 is the amino acid sequence an exemplary human CCL2 protein. QPDAINAPVTCCYNFTNRKISVQRLASYRRITSSKCPKEAVIFKTIVAKEICADPKQKWVQDS MDHLDKQTQTPKT SEQ ID NOs: 9-20 are nucleic acid primer sequences (see Table 3). DETAILED DESCRIPTION I. Abbreviations ACTA2 actin alpha 2 CCL C-C motif chemokine ligand COL1A1 collagen type 1 alpha 1 CXCL C-X-C motif chemokine ligand DCN decorin ECM extracellular matrix ELR Glu-Leu-Arg FN1 fibronectin 1 GAPDH glyceraldehyde-3-phosphatge dehydrogenase IL interleukin LOX lysyl oxidase mRSS modified Rodnan’s Skin Score pSMAD phosphor-SMAD SSc systemic sclerosis (scleroderma) TGF-β transforming growth factor-beta8123-112369-02 05552TNC tenascin C II. Summary of Terms Unless otherwise noted, technical terms are used according to conventional usage. Definitions of many common terms in molecular biology may be found in Krebs et al. (eds.), Lewin’s genes XII, published by Jones & Bartlett Learning, 2017. As used herein, the singular forms “a,” “an,” and “the,” refer to both the singular as well as plural, unless the context clearly indicates otherwise. For example, the term “a peptide” includes singular or plural antigens and can be considered equivalent to the phrase “at least one peptide.” As used herein, the term “comprises” means “includes.” It is further to be understood that any and all base sizes or amino acid sizes, and all molecular weight or molecular mass values, given for nucleic acids or polypeptides are approximate, and are provided for descriptive purposes, unless otherwise indicated. Although many methods and materials similar or equivalent to those described herein can be used, particular suitable methods and materials are described herein. In case of conflict, the present specification, including explanations of terms, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. To facilitate review of the various aspects, the following explanations of terms are provided: Administration: The introduction of a composition (such as a protein or peptide) into a subject by a chosen route. For example, if the chosen route is intravenous, the composition is administered by introducing the composition into a vein of the subject. Exemplary routes of administration include, but are not limited to, injection (such as intraocular, subcutaneous, intramuscular, intradermal, intraperitoneal, and intravenous), oral, intraductal, sublingual, transdermal, intranasal, topical, inhalation routes and via a medical implant. In some examples herein, the disclosed chemokine cocktails are formulated for topical, intranasal, inhalation, intravenous, intramuscular, intradermal, or subcutaneous administration. Biologically active fragments or variants (of a chemokine protein): Any fragment, derivative, homolog or analog of a chemokine protein that possesses an in vivo or in vitro activity that is characteristic of the chemokine itself (such as anti-fibrotic activity or pro-ECM production activity). In some aspects, the biologically active fragment or variant possesses at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or greater of the biological activity of the native (full-length) chemokine. In some examples, the fragment is at least 30, at least 40, at least 50, at least 60, or at least 70 amino acids in length. In some examples, the fragment is about 5, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45 or about 50 amino acids shorter than the native (full-length) chemokine. In some examples, the amino acid sequence of the8123-112369-02 05552variant is at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to any one of SEQ ID NOs: 1-8. C-C motif chemokine ligand 2 (CCL2): A member of the CC chemokine subfamily characterized by two adjacent cysteine residues. CCL2 displays chemotactic activity for monocytes and basophils but not for neutrophils or eosinophils. It has been implicated in the pathogenesis of diseases characterized by monocytic infiltrates, such as psoriasis, rheumatoid arthritis and atherosclerosis. It binds to chemokine receptors CCR2 and CCR4. Elevated expression of the encoded protein is associated with severe acute respiratory syndrome coronavirus 2. Exemplary CCL2 amino acid sequences are publicly available, including human CCL2 sequences, such as under NCBI Gene ID 6347. An exemplary CCL2 amino acid sequence is set forth herein as SEQ ID NO: 8. C-X-C motif chemokine ligand 1 (CXCL1): A member of the CXC subfamily of chemokines. The CXCL1 protein is a secreted growth factor that signals through the G-protein coupled receptor, CXC receptor 2 (CXCR2). This protein plays a role in inflammation and as a chemoattractant for neutrophils. Aberrant expression of CXCL1 is associated with the growth and progression of certain tumors. A naturally occurring processed form of this protein has increased chemotactic activity. Exemplary CXCL1 amino acid sequences are publicly available, including human CXCL1 sequences, such as under NCBI Gene ID 2919. An exemplary CXCL1 amino acid sequence is set forth herein as SEQ ID NO: 1. C-X-C motif chemokine ligand 4 (CXCL4): A member of the CXC chemokine family. CXCL4 is released from the alpha granules of activated platelets in the form of a homotetramer which has high affinity for heparin and is involved in platelet aggregation. This protein is chemotactic for numerous other cell types and also functions as an inhibitor of hematopoiesis, angiogenesis and T-cell function. CXCL4 also exhibits antimicrobial activity against Plasmodium falciparum. CXCL4 is also known as platelet factor 4 (PF4). Exemplary CXCL4 amino acid sequences are publicly available, including human CXCL4 sequences, such as under NCBI Gene ID 5196. An exemplary CXCL4 amino acid sequence is set forth herein as SEQ ID NO: 2. C-X-C motif chemokine ligand (CXCL8): A member of the CXC chemokine family and a major mediator of the inflammatory response. CXCL8 is secreted by mononuclear macrophages, neutrophils, eosinophils, T lymphocytes, epithelial cells, and fibroblasts. It functions as a chemotactic factor by guiding neutrophils to the site of infection. CXCL8 also participates with other cytokines in the proinflammatory signaling cascade and plays a role in systemic inflammatory response syndrome (SIRS). CXCL8 is believed to play a role in the pathogenesis of bronchiolitis, coronary artery disease and endothelial dysfunction. The overproduction of CXCL8 protein is also thought to cause the lung inflammation associated with cystic fibrosis. The CXL8 protein is also secreted by tumor cells and promotes tumor migration, invasion, angiogenesis and metastasis. CXCL8 is also known as interleukin-8 (IL-8). Exemplary CXCL8 amino acid sequences are publicly available, including8123-112369-02 05552human CXCL8 sequences, such as under NCBI Gene ID 3576. An exemplary CXCL8 amino acid sequence is set forth herein as SEQ ID NO: 3. C-X-C motif chemokine ligand (CXCL9): A member of the CXC chemokine superfamily that encodes secreted proteins involved in immunoregulatory and inflammatory processes. The CXCL9 protein is thought to be involved in T cell trafficking. CXCL9 binds to C-X-C motif chemokine 3 (CXCR3) and is a chemoattractant for lymphocytes but not for neutrophils. Exemplary CXCL9 amino acid sequences are publicly available, including human CXCL9 sequences, such as under NCBI Gene ID 4283. An exemplary CXCL9 amino acid sequence is set forth herein as SEQ ID NO: 4. C-X-C motif chemokine ligand (CXCL10): A chemokine of the CXC subfamily and ligand for the receptor CXCR3. Binding of this protein to CXCR3 results in pleiotropic effects, including stimulation of monocytes, natural killer and T-cell migration, and modulation of adhesion molecule expression. CXCL10 is also known as IP-10. Exemplary CXCL10 amino acid sequences are publicly available, including human CXCL10 sequences, such as under NCBI Gene ID 3627. An exemplary CXCL10 amino acid sequence is set forth herein as SEQ ID NO: 5. C-X-C motif chemokine ligand (CXCL11): A member of the CXC chemokine superfamily. CXCL11 induces a chemotactic response in activated T-cells and is the dominant ligand for CXCR3. IFN-γ is a potent inducer of transcription of this gene. Exemplary CXCL11 amino acid sequences are publicly available, including human CXCL11 sequences, such as under NCBI Gene ID 6373. An exemplary CXCL11 amino acid sequence is set forth herein as SEQ ID NO: 6. C-X-C motif chemokine ligand (CXCL12): A stromal cell-derived alpha chemokine member of the intercrine family. The CXCL12 protein functions as a ligand for the G-protein coupled receptor CXCR4, and plays a role in many diverse cellular functions, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis. Mutations in the CXCL12 gene are associated with resistance to human immunodeficiency virus type 1 infections. Exemplary CXCL12 amino acid sequences are publicly available, including human CXCL12 sequences, such as under NCBI Gene ID 6387. An exemplary CXCL12 amino acid sequence is set forth herein as SEQ ID NO: 7. Chemical modification (of a chemokine): Includes any modification to a chemokine protein carried out by a chemical reaction. Chemical modifications do not result in a change to the primary amino acid sequence of the protein. In some aspects, the chemical modification increases stability (inhibits degradation) or increases half-life of the protein. In some examples, the chemical modification is at the N-terminus of the peptide, the C-terminus of the peptide, or both. Exemplary N-terminal modifications include formylation, acetylation, propionylation, pyroglutamate formation, myristoylation, palmitylation, S-palmitoylation, mono-methylation, di-methylation, tri-methylation, or any combination thereof. Exemplary C-terminal modifications include methylation, alpha-amidation,8123-112369-02 05552or a combination thereof. In some aspects, the chemical modification is a non-standard peptide linkage, a non-canonical amino acid or a D-amino acid. In some examples, the non-canonical amino acid is a methylated amino acid, an amino acid conjugated to a polyethylene glycol polymer, an amino acid conjugated to biotin, an amino acid conjugated to fluorescein isothiocyanate (FITC), an amino acid conjugated to a carrier protein, an amino acid labelled with a radioactive isotope, or any combination thereof. In some examples, the methylated amino acid is a mono-methylated amino acid, di-methylated amino acid, or tri-methylated amino acid. In some examples, the carrier protein is bovine serum albumin, ovalbumin, or keyhole limpet hemocyanin. In some examples, the radioactive isotope is2H,15N,13C, or both15N and13C. Chemokine cocktail: Refers to a composition that includes at least two different chemokine proteins, such as 2, 3, 4, 5, 6, 7, or 8 different chemokine proteins, or biologically active fragments or variants thereof. In some examples, the chemokine cocktail includes two chemokines (e.g., CXCL1 and CXCL8), three chemokines (e.g., CXCL1, CXCL8 and CCL2), four chemokines (e.g., CXCL4, CXCL9, CXCL10 and CXCL11) or five chemokines (e.g., CXCL4, CXCL9, CXCL10, CXCL11 and CXCL12), or biologically active fragments or variants thereof. Conservative variants: "Conservative" amino acid substitutions are those substitutions that do not substantially affect or decrease an activity or antigenicity of a protein or peptide. For example, a protein or peptide disclosed herein can include at most about 1, at most about 2, at most about 3, at most about 4, at most about 5, at most about 6, at most about 7, at most about 8, at most about 9, or at most about 10 conservative substitutions (such as 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 conservative substitutions, and retain biological activity, such as the ability to inhibit fibrosis or increase ECM production). Specific, non-limiting examples of a conservative substitution include the following examples: Original Residue Conservative Substitutions Ala Ser Arg Lys Asn Gln, His Asp Glu Cys Ser Gln Asn Glu Asp His Asn; Gln Ile Leu, Val Leu Ile; Val Lys Arg; Gln; Glu8123-112369-02 05552Met Leu; Ile Phe Met; Leu; Tyr Ser Thr Thr Ser Trp Tyr Tyr Trp; Phe Val Ile; Leu The term conservative variant also includes the use of a substituted amino acid in place of an unsubstituted parent amino acid. Non-conservative substitutions are those that reduce an activity or antigenicity. Effective amount: A quantity of a specific substance (such as a chemokine or chemokine cocktail) sufficient to achieve a desired effect in a subject being treated. When administered to a subject, a dosage will generally be used that will achieve target tissue concentrations that have been shown to achieve a desired in vitro effect. “Effective amount” can also be referred to as “therapeutically effective amount.” In some aspects herein, the effective amount is an amount of a chemokine or chemokine cocktail capable of reducing or inhibiting fibrosis of a particular organ / tissue by at least 10%, at least 20%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, or even 100%, for example as compared to fibrosis present prior to treatment. In other aspects, the effective amount is an amount of a chemokine or chemokine cocktail capable of increasing ECM production by at least 10%, at least 20%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, or even 100%, such as compared to ECM production prior to treatment. In some aspects, the effective amount is an amount of a chemokine or chemokine cocktail capable of promoting wound closure by at least 10%, at least 20%, at least 50%, at least 75%, at least 80%, at least 90%, at least 95%, or even 100%, such as compared to wound closure prior to treatment. Extracellular matrix (ECM): A non-cellular network of proteins and other molecules (e.g., extracellular macromolecules, collagen, enzymes, glycoproteins) that surround, support and provide structure to cells and tissues of the body. Fibrosis: A condition associated with the thickening and scarring of connective tissue. Often, fibrosis occurs in response to an injury, such as from a disease or condition that damages tissue. Fibrosis is an exaggerated wound healing response that when severe, can interfere with normal organ function. Fibrosis can occur in almost any tissue of the body, including in the lung (pulmonary fibrosis, cystic fibrosis, radiation-induced lung injury), liver (cirrhosis, biliary atresia), heart (arterial fibrosis, endomyocardial fibrosis, prior myocardial infarction), brain, skin (scleroderma, sclerosis), kidney, joints and intestine (Crohn’s disease). A ”fibrosis-related disease or fibrotic disease” is a disease or disorder in which fibrosis is a primary pathologic basis, result or symptom. Fibrosis-related diseases include, for example, skin8123-112369-02 05552pathologic scarring, such as colloid and hypertrophic scarring; cirrhosis, such as cirrhosis of the liver or gallbladder; cardiac fibrosis; liver fibrosis; kidney fibrosis; pulmonary fibrosis; bone-marrow fibrosis; rheumatic heart disease; sclerosing peritonitis; glomerulosclerosis and scleroderma. Fibrosis can be the result of a number of factors. For instance, fibrosis can be induced by adrenergic and / or angiotension receptor signaling, and, therefore, can be induced by agonists of adrenergic or angiotensin receptors. Such agonists include, for example, angiotensin II and phenylephrine. Fibrosis can also be induced by tissue injury. As used herein, “tissue injury” refers to any damage of or strain placed on a tissue such that there is a change that occurs in or to the tissue. Inhibiting: Reducing, such as a disease or disorder or symptom thereof. The inhibition of a disease or disorder can decrease one or more signs or symptoms of the disease or disorder. Isolated: An “isolated” or “purified” biological component (such as a nucleic acid or peptide) has been substantially separated, produced apart from, or purified away from other biological components in the cell of the organism in which the component naturally occurs, that is, other chromosomal and extra-chromosomal DNA and RNA, and proteins. Nucleic acids, peptides and proteins that have been “isolated” or “purified” thus include nucleic acids and proteins purified by standard purification methods. The term also embraces nucleic acids, peptides and proteins prepared by recombinant expression in a host cell, as well as chemically synthesized nucleic acids or proteins. The term “isolated” or “purified” does not require absolute purity; rather, it is intended as a relative term. Peptide, polypeptide or protein: A polymer in which the monomers are amino acid residues which are joined together through amide bonds. When the amino acids are alpha-amino acids, either the L-optical isomer or the D-optical isomer can be used, the L-isomers being preferred. The terms “polypeptide,” “peptide,” or “protein” as used herein are intended to encompass any amino acid sequence and include modified sequences such as glycoproteins. The terms “protein,” “polypeptide” and “peptide” are specifically intended to cover naturally occurring proteins, as well as those which are recombinantly or synthetically produced. Pharmaceutically acceptable carriers: The pharmaceutically acceptable carriers of use are conventional. Remington: The Science and Practice of Pharmacy, 23nded., London, UK: Academic Press, 2020, describes compositions and formulations suitable for pharmaceutical delivery of the proteins disclosed herein. In general, the nature of the carrier will depend on the particular mode of administration being employed. For instance, parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle. For solid compositions (such as powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate. In addition to biologically neutral carriers, pharmaceutical compositions to be administered can contain8123-112369-02 05552minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate. Sequence identity: The similarity between amino acid or nucleic acid sequences is expressed in terms of the similarity between the sequences, otherwise referred to as sequence identity. Sequence identity is frequently measured in terms of percentage identity (or similarity or homology); the higher the percentage, the more similar the two sequences. Homologs or variants of a polypeptide or nucleic acid molecule will possess a relatively high degree of sequence identity when aligned using standard methods. Methods of alignment of sequences for comparison are well-known. Various programs and alignment algorithms are described in: Smith and Waterman, Adv. Appl. Math.2:482, 1981; Needleman and Wunsch, J. Mol. Biol.48:443, 1970; Pearson and Lipman, Proc. Natl. Acad. Sci. U.S.A. 85:2444, 1988; Higgins and Sharp, Gene 73:237, 1988; Higgins and Sharp, CABIOS 5:151, 1989; Corpet et al., Nucleic Acids Research 16:10881, 1988; and Pearson and Lipman, Proc. Natl. Acad. Sci. U.S.A. 85:2444, 1988. Altschul et al., Nature Genet.6:119, 1994, presents a detailed consideration of sequence alignment methods and homology calculations. The NCBI Basic Local Alignment Search Tool (BLAST) (Altschul et al., J. Mol. Biol.215:403, 1990) is available from several sources, including the National Center for Biotechnology Information (NCBI, Bethesda, MD) and on the internet, for use in connection with the sequence analysis programs blastp, blastn, blastx, tblastn and tblastx. A description of how to determine sequence identity using this program is available on the NCBI website on the internet. Homologs and variants of a protein are typically characterized by possession of at least about 75%, for example at least about 80%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity counted over the full length alignment with the amino acid sequence of the protein using the NCBI Blast 2.0, gapped blastp set to default parameters. For comparisons of amino acid sequences of greater than about 30 amino acids, the Blast 2 sequences function is employed using the default BLOSUM62 matrix set to default parameters, (gap existence cost of 11, and a per residue gap cost of 1). When aligning short peptides (fewer than around 30 amino acids), the alignment should be performed using the Blast 2 sequences function, employing the PAM30 matrix set to default parameters (open gap 9, extension gap 1 penalties). Proteins with even greater similarity to the reference sequences will show increasing percentage identities when assessed by this method, such as at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity. When less than the entire sequence is being compared for sequence identity, homologs and variants will typically possess at least 80% sequence identity over short windows of 10-20 amino acids, and may possess sequence identities of at least 85% or at least 90% or 95% depending on their similarity to the reference sequence. Methods for8123-112369-02 05552determining sequence identity over such short windows are available at the NCBI website on the internet. Subject: Living multi-cellular vertebrate organisms, a category that includes both human and veterinary subjects, including human and non-human mammals. Synthetic: Produced by artificial means in a laboratory, for example a synthetic nucleic acid or peptide can be chemically synthesized in a laboratory. Treating, treatment, and therapy: Any success or indicia of success in the attenuation or amelioration of an injury, pathology or condition, including any objective or subjective parameter such as abatement, remission, diminishing of symptoms or making the condition more tolerable to the patient, slowing in the rate of degeneration or decline, making the final point of degeneration less debilitating, improving a subject’s physical or mental well-being. The treatment may be assessed by objective or subjective parameters; including the results of a physical examination, laboratory tests, neurological examination, or psychiatric evaluations. Wound: An injury or damage to living tissue. Wound repair: The process of replacing damaged or missing cellular structures or tissue layers. Wound repair (or wound healing) is characterized by the steps of hemostasis (blood clotting), inflammation, proliferation (growth of new tissues) and remodeling. III. Introduction Chemokines are a class of signaling molecules that influence cellular functions including chemotaxis, survival, proliferation, organ development, inflammation, and tissue remodeling through interactions with cell surface receptors and ECM molecules (Blaschitz et al., Placenta 2015, 36:1333- 6; Ekert et al., Fibrogenesis Tissue Repair 2011, 4:23). C-X-C chemokines are named for the four highly conserved cysteine residues on the NH2terminus, with the first two cysteine residues being separated by a variable, “X”, amino acid residue (Clark-Lewis et al., J Biol Chem 1994, 269:16075- 81; Covell et al., Protein Sci 1994, 3:2064-72). The general structure consists of an N-terminal region, anti-parallel β-sheets, and an α-helix near the C-terminus. The function of CXC chemokines in angiogenesis is dictated by the presence or absence of an “ELR” motif (composed of the amino acids Glu-Leu-Arg) adjacent to the first cysteine residue (Strieter et al., J Biol Chem 1995, 270:27348-57). ELR-positive (ELR+) CXC chemokine ligands are pro-angiogenic and include: CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, CXCL8, and CXCL12 (Romagnani et al., Trends Immunol 2004, 25:201-9). The ELR-negative (ELR-) CXC chemokine ligands, including CXCL4, CXCL9, CXCL10, and CXCL11, elicit mostly angiostatic effects, limiting the proliferative response to growth factors (Strieter et al., J Biol Chem 1995, 270:27348-57; Shiraha et al., J Cell Biol 1999, 146:243-54; Bodnar et al., J Cell Sci 2009, 122:2064- 77).8123-112369-02 05552ELR- chemokines have amino acid sequence similarity, yet their function and role in evolution and tissue remodeling are distinct. During the late stages of wound healing after injury, CXCL9, CXCL10, and CXCL11 have been shown to prevent overactive remodeling and promote maturation, acting as a stop signal through CXCR3 signaling (Yates et al., Am J Pathol 2007, 171:484-95; Yates et al., Am J Pathol 2008, 173:643-52; Yates et al., Wound Repair Regen 2009, 17:34-41; Yates et al., Am J Pathol 2010, 176:1743-55). The administration of either CXCL10 or CXCL11 inhibits bleomycin-induced pulmonary fibrosis in mice (Tager et al., Am J Respir Cell Mol Biol 2004, 31:395-404; Burdick et al., Am J Respir Crit Care Med 2005, 171:261-8) and CXCL9 inhibits liver fibrosis (Sahin et al., Hepatology 2012, 55:1610-9). However, CXCL4, which also acts as a ligand for CXCR3, promotes liver fibrosis (Zaldivar et al., Hepatology 2010, 51:1345-53) and is a biomarker for SSc (van Bon et al., N Engl J Med 2014, 370:433-43). ELR+ chemokines, including CXCL1, CXCL8, and the C-C chemokine CCL2, are pro- angiogenic chemokines. In the context of fibrosis, CXCL1 promotes cardiac remodeling (Wang et al., Eur Heart J 2018, 39:1818-31). CXCL1 and CXCL8 levels are increased in serum from SSc patients (Furuse et al., J Rheumatol 2003, 30:1524-8) and there is a significant interaction between a polymorphism in the CXCL8 gene and an increased risk for SSc (Lee et al., Arthritis Rheum 2007, 56:2443-8). CXCL8 decreases gene expression of the anti-fibrotic matrikine, decorin (Cabello- Verrugio et al., J Biol Chem 2012, 287:6773-87; Wu et al., Eur J Med Res 2007, 12:360-8). CCL2 has been linked to the development and progression of fibrosis. CCL2 attracts monocytes to the wound site, promotes the expression of TGF-β, and enhances fibroblast collagen expression in an autocrine and juxtacrine manner (Gharaee-Kermani et al., J Biol Chem 1996, 271:17779-84). CCL2 is associated with enhanced liver (Marra Fet al., Am J Pathol 1998, 152:423-30), lung (Inoshima et al., Am J Physiol Lung Cell Mol Physiol 2004, 286:L1038-44), kidney (Tesch et al., J Clin Invest 1999, 103:73-80), and skin (Hasegawa et al., Clin Exp Immunol 1999, 117:159-65; Yamamoto and Nishioka, J Invest Dermatol 2003, 121:510-6) fibrosis. CCL2 significantly induces type I collagen, hyaluronan production (Kim et al., J Cosmet Dermatol 2014, 13:44-51), alpha1(I) collagen expression (Yamamoto and Nishioka, J Invest Dermatol 2003, 121:510-6), collagen IV expression (Park et al., Am J Physiol Renal Physiol 2008, 295:F749-57), and proper collagen fibril alignment, arrangement, and sizing (Ferreira et al., J Invest Dermatol 2006, 126:1900-8). CXCL12 promotes fibrosis in animal models of pulmonary and liver disease (Makino et al., J Med Invest 2013, 60:127-37; Akcora et al., Biochim Biophys Acta Mol Basis Dis 2018, 1864:804-18) and can directly increase expression of connective tissue growth factor (CTGF) (Lin et al., J Biomed Sci 2018, 25:19; Lin et al., PLoS One 2014, 9:e104746) and secretion of procollagen I (Patalano et al., Sci Rep 2018, 8:3499). Expression of CXCL12 is elevated in SSc patients with early disease (Cipriani et al., Arthritis Rheum 2006, 54:3022-33). However, exogenous expression of CXCL12 may provide a protective role in cardiac fibrosis (Tang et al., Mol Biol Rep 2010, 37:1957-69).8123-112369-02 05552Fibroblasts are the effector cells in skin fibrosis. Mechanistically, fibroblasts are attracted to sites of injury by chemokines such as CCL2 that often arise from resident cells through the epithelial / endothelial mesenchymal transition (Yan et al., Am J Pathol 2010, 176:2247-58; Sun et al., Am J Physiol Lung Cell Mol Physiol 2011, 300:L341-53; Barbhuiya et al., Oncotarget 2017, 8:101520-34). When tissue is injured, resident tissue fibroblasts become activated by growth factors, such as TGF-β. Activated fibroblasts secrete inflammatory mediators, are highly contractile, synthesize and secrete ECM molecules (collagen, fibronectin, and laminin) during the proliferative stage of wound healing. Tissue remodeling follows a transient increase in ECM deposition which is quickly followed by efficient tissue remodeling after which tissue function / structure is restored. However, after recurring damage, fibroblast ECM production becomes excessive with high likelihood of organ failure. Chemokines, such as CXCL5, CXCL8, and CXCL12, exasperate this process by increasing fibroblast contractility, upregulating fibroblast conversion, and increasing the production of ECM proteins such as collagen and tenascin (Schauer et al., Urology 2008, 72:205-13; Gharaee- Kermani et al., PLoS One 2012, 7:e49278). To address fibrotic manifestation at its source, recent research has investigated mechanisms of growth factor-induced upregulation of ECM production and possible convergent pathways where chemokines and cytokines may intercede. Due to their disease relevance, small size, and pleiotropic signaling effects, chemokines are potentially attractive as therapeutic targets (Solari et al., Eur J Pharmacol 2015, 746:363-7; Trivedi et al., J Crohns Colitis 2018, 12:1508). Although the role and mechanisms of individual chemokines and cytokines on fibroblast matrix production have been dissected, little is known of chemokine combination synergistic actions. Detailing their synergy through the investigation of cocktail combination therapies in individualized medicine is highly needed. The flaws of individual therapies enhance the need to perform mechanistic chemokine cocktail combination studies (Yang et al., Cancer Immunol Immunother 2013, 62:1649-62). Related to wound healing, harnessing of chemokine cocktails appears to have a high therapeutic benefit for adherent tissue remodeling, of which no current treatments can reverse this cascade (Becker et al., Hautarzt 2019, 70:723-41). In the context of fibrosis therapies, most translational monotherapy approaches have not shown promising results as expected (Yang et al., Cancer Immunol Immunother 2013, 62:1649-62; Ding and Tredgetm Adv Wound Care (New Rochelle) 2015, 4:673-86). To the contrary, in preclinical models, cytokine cocktails show very promising anti-tumor effects (Yang et al., Cancer Immunol Immunother 2013, 62:1649-62). In clinical trials, immune treatment with dendritic cells stimulated with cytokine cocktails have a prolonged survival effect in tumor bearing patients (Mitsuya et al., Anticancer Res 2020, 40:6473-84; Laureano et al., Oncoimmunology 2022, 11:2096363). Therefore, the utility of a chemokine cocktail therapy is evidenced on the promising results seen in cancer clinical trials more than in individual therapies (Yang et al., Cancer Immunol Immunother 2013, 62:1649-62). To summarize, chemokine combinations that act on the same or different receptors are attractive8123-112369-02 05552therapeutic targets to exhibit precise, synergistic effects on downstream signaling (Cecchinato et al., J Leukoc Biol 2016, 99:851-5; Proudfoot and Uguccioni, Front Immunol 2016, 7:183; Williams et al., Thorax 2017, 72:66-73). The effects of chemokines and custom chemokine cocktails were evaluated on ECM production of quiescent and TGF-activated fibroblasts. IV. Methods of Treating or Inhibiting Fibrosis Fibrosis is the result of excessive extracellular matrix (ECM) deposition. Fibrosis arises from several etiologies including autoimmune disease, persistent infections, chemical insult, and tissue injury. Fibroblasts, the primary producers of ECM, are influenced by a multitude of circulating signals and cellular response mechanisms, including chemokines. There are different chemokine subtypes, including the C-X-C and C-C chemokine families. These are important biomarkers of fibrotic disease and are necessary for proper wound healing, but little is known of their synergistic effects in combination therapies. The studies disclosed herein aim to distinguish the role of known chemokine- derived cellular response mechanisms from their synergistic effects on fibroblast-ECM production. Results disclosed herein show that transforming growth factor-beta (TGF-β) activated human dermal fibroblasts with single chemokines or chemokine combination cocktails using similar structure and receptor pairing. Analysis of ECM gene expression and protein immunoblot quantification revealed that CXCL8 and the CXCL1+CXCL8+CCL2 chemokine cocktails reduce TGF-β stimulated fibroblast production of COL1a1 and TNC mRNA, but elevate fibronectin, decorin, and pSMAD protein levels after 24 hours. RNA-Sequencing identified a gene enrichment relationship between TGF-β and CXCL8, particularly associated with ECM cell-substrate junctions and collagen formation / biosynthesis. These findings suggest a synergistic role of CXCL8, CXCL1, and CCL2 in TGF-β-stimulated fibroblast ECM production in the wound healing response. Provided herein are methods of treating or inhibiting fibrosis in a subject. In some aspects, the method includes administering to the subject an effective amount of a chemokine cocktail that includes two or more (such as two, three or all four) of a CXCL4 protein, a CXCL9 protein, a CXCL10 protein, and a CXCL11 protein, or biologically active fragments or variants thereof; two or more (such as two, three, four or all five) of a CXCL4 protein, a CXCL9 protein, a CXCL10 protein, a CXCL11 protein and a CXCL12 protein, or biologically active fragments or variants thereof; or a CXCL1 protein and a CXCL8 protein, or biologically active fragments or variants thereof. In some aspects, the CXCL1, CXCL4, CXCL8, CXCL9, CXCL10, CXCL11, and / or CXCL12 proteins are human proteins. In other aspects, the CXCL1, CXCL4, CXCL8, CXCL9, CXCL10, CXCL11, and / or CXCL12 proteins are from a non-human species, such as mouse, rat, or non-human primate. In some aspects, the CXCL1, CXCL4, CXCL8, CXCL9, CXCL10, CXCL11, and / or CXCL12 protein includes at least one chemical modification. In some examples, the at least one8123-112369-02 05552chemical modification is at the N-terminus, the C-terminus, or both. In specific examples, the N- terminal modification includes formylation, acetylation, propionylation, pyroglutamate formation, myristoylation, palmitylation, S-palmitoylation, mono-methylation, di-methylation, tri-methylation, or any combination thereof. In specific examples, the C-terminal modification includes methylation, alpha-amidation, or a combination thereof. Other chemical modifications include, for example, a non- standard peptide linkage, a D-amino acid, or a non-canonical amino acid (e.g., a methylated amino acid, an amino acid conjugated to a polyethylene glycol polymer, an amino acid conjugated to biotin, an amino acid conjugated to FITC, an amino acid conjugated to a carrier protein, an amino acid labelled with a radioactive isotope). In some aspects, the amino acid sequence of the CXCL1 protein is at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1. In some examples, the amino acid sequence of the CXCL1 protein includes or consists of SEQ ID NO: 1. In some aspects, the amino acid sequence of the CXCL4 protein is at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2. In some examples, the amino acid sequence of the CXCL4 protein includes or consists of SEQ ID NO: 2. In some aspects, the amino acid sequence of the CXCL8 protein is at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 3. In some examples, the amino acid sequence of the CXCL8 protein includes or consists of SEQ ID NO: 3. In some aspects, the amino acid sequence of the CXCL9 protein is at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%identical to SEQ ID NO: 4. In some examples, the amino acid sequence of the CXCL9 protein includes or consists of SEQ ID NO: 4. In some aspects, the amino acid sequence of the CXCL10 protein is at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 5. In some examples, the amino acid sequence of the CXCL10 protein includes or consists of SEQ ID NO: 5. In some aspects, the amino acid sequence of the CXCL11 protein is at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 6. In some examples, the amino acid sequence of the CXCL11 protein includes or consists of SEQ ID NO: 6. In some aspects, the amino acid sequence of the CXCL12 protein is at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to8123-112369-02 05552SEQ ID NO: 7. In some examples, the amino acid sequence of the CXCL12 protein includes or consists of SEQ ID NO: 7. In some examples, the chemokine cocktail includes two or more (such as two, three or all four) of a CXCL4 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 6. In some examples, the chemokine cocktail includes or consists of a CXCL4 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 6. In specific examples, the chemokine cocktail includes two or more (such as two, three, or all four) of a CXCL4 protein having an amino acid sequence including or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence including or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence including or consisting of SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence including or consisting of SEQ ID NO: 6. In other specific examples, the chemokine cocktail includes or consists of a CXCL4 protein having an amino acid sequence including or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence including or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence including or consisting of SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence including or consisting of SEQ ID NO: 6. In some examples, the chemokine cocktail includes two or more (such as two, three, four or all five) of a CXCL4 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at8123-112369-02 05552least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 6; and a CXCL12 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 7. In some examples, the chemokine cocktail includes or consists of a CXCL4 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 6; and a CXCL12 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 7. In specific examples, the chemokine cocktail includes two or more (such as two, three, four or all five) of a CXCL4 protein having an amino acid sequence including or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence including or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence including or consisting of SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence including or consisting of SEQ ID NO: 6; and a CXCL12 protein having an amino acid sequence including or consisting of SEQ ID NO: 7. In other specific examples, the chemokine cocktail includes or consists of a CXCL4 protein having an amino acid sequence including or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence including or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence including or consisting of SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence including or consisting of SEQ ID NO: 6; and a CXCL12 protein having an amino acid sequence including or consisting of SEQ ID NO: 7. In some examples, the chemokine cocktail includes a CXCL1 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1; and a CXCL8 protein having an amino acid sequence at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 3. In specific examples, the chemokine cocktail includes or consists of a CXCL1 protein having an amino acid sequence including or consisting of SEQ ID NO: 1; and a CXCL8 protein having an amino acid sequence including or consisting of SEQ ID NO: 3.8123-112369-02 05552In some aspects of the methods, the fibrosis is fibrosis of the skin, lung, heart, kidney or liver (or any other tissue). In some examples, the subject has scleroderma, pulmonary fibrosis, idiopathic pulmonary fibrosis, morphea, fibrosis as a result of graft-versus-host disease (GVHD), a keloid or hypertrophic scar, subepithelial fibrosis, endomyocardial fibrosis, uterine fibrosis, myelofibrosis, retroperitoneal fibrosis, nephrogenic systemic fibrosis, scarring after surgery, asthma, cirrhosis / liver fibrosis, aberrant wound healing, glomerulonephritis, or multifocal fibrosclerosis. In some examples, the method treats the systemic form of scleroderma, such as limited cutaneous scleroderma or diffuse cutaneous scleroderma (or systemic sclerosis). The methods can also be used to treat the localized form of scleroderma, including morphea and linear scleroderma. In some aspects, the method further includes selecting a subject in need of treatment, such as a subject with a fibrotic disease, such as scleroderma, idiopathic pulmonary fibrosis, morphea, a keloid scar, a hypertrophic scar, or subepithelial fibrosis. In exemplary applications, compositions are administered to a subject having a fibrotic disease, such as scleroderma, idiopathic pulmonary fibrosis, morphea, a keloid scar, a hypertrophic scar, or subepithelial fibrosis, or any of the disorders listed above, in an amount sufficient to reduce the fibrosis. Amounts effective for this use will depend upon the severity of the disease, the general state of the patient's health, and the robustness of the patient’s immune system. In one example, a therapeutically effective amount of the compound is that which provides either subjective relief of a symptom(s) or an objectively identifiable improvement as noted by the clinician or other qualified observer. In some aspects of the disclosed methods, the subject is human. V. Methods of Treating Wounds and Increasing ECM Production Also provided herein are methods of increasing extracellular matrix (ECM) production and / or treating a wound in a subject. In some aspects, the method includes administering to the subject an effective amount of a chemokine cocktail that includes a CXCL1 protein and a CXCL8 protein, or biologically active fragments or variants thereof; or a CXCL1 protein, a CXCL8 protein, and a CCL2 protein, or biologically active fragments or variants thereof. In some aspects, the CXCL1, CXCL8 and / or CCL2 proteins are human proteins. In other aspects, the CXCL1, CXCL8 and / or CCL2 proteins are from a non-human species, such as mouse, rat, or non-human primate. In some aspects, the CXCL1, CXCL8 and / or CCL2 protein includes at least one chemical modification. In some examples, the at least one chemical modification is at the N-terminus, the C- terminus, or both. In specific examples, the N-terminal modification includes formylation, acetylation, propionylation, pyroglutamate formation, myristoylation, palmitylation, S-palmitoylation, mono-methylation, di-methylation, tri-methylation, or any combination thereof. In specific examples, the C-terminal modification includes methylation, alpha-amidation, or a combination thereof. Other8123-112369-02 05552chemical modifications include, for example, a non-standard peptide linkage, a D-amino acid, or a non-canonical amino acid (e.g., a methylated amino acid, an amino acid conjugated to a polyethylene glycol polymer, an amino acid conjugated to biotin, an amino acid conjugated to FITC, an amino acid conjugated to a carrier protein, an amino acid labelled with a radioactive isotope). In some examples, the amino acid sequence of the CXCL1 protein is at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 1; the amino acid sequence of the CXCL8 protein is at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 3; and / or the amino acid sequence of the CCL2 protein is at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to SEQ ID NO: 8. In specific examples, the amino acid sequence of the CXCL1 protein includes or consists of SEQ ID NO: 1; the amino acid sequence of the CXCL8 protein includes or consists of SEQ ID NO: 3; and / or the amino acid sequence of the CCL2 protein includes or consists of SEQ ID NO: 8. In some aspects of the method, the chemokine cocktail is administered locally to the site of a wound. In some aspects, the wound is a surgical wound. In some examples, the surgical wound is an anastomotic wound caused by a surgical procedure. These methods can include administration of an effective amount of a chemokine cocktail, as disclosed herein, to an individual before, after, and / or during anastomotic or other surgery. Anastomosis is the connecting of two tubular structures, for example, when a mid-section of intestine is removed and the remaining portions are linked together to reconstitute the intestinal tract. In other aspects, the wound is a non-surgical traumatic wound. Other examples of wounds include, but are not limited to, excisional wounds, deep wounds involving damage of the dermis and epidermis, eye tissue wounds, dental tissue wounds, oral cavity wounds, diabetic ulcers, dermal ulcers, cubitus ulcers, arterial ulcers, venous stasis ulcers, burns resulting from heat exposure or chemicals, or wounds resulting from ischemia and ischemic injury, such as chronic venous leg ulcers caused by an impairment of venous circulatory system return and / or insufficiency. In some examples of the disclosed methods, an effective amount of a chemokine cocktail, as disclosed herein, is an amount sufficient to promote dermal reestablishment subsequent to dermal loss, or an amount sufficient to increase the tensile strength of epidermis and epidermal thickness. Methods are also provided herein to increase the adherence of skin grafts to a wound bed and to stimulate re-epithelialization from the wound bed. Types of grafts include, but are not limited to autologous skin graft, artificial skin, allografts, autodermic grafts, autoepidermic grafts, avacular grafts, Blair-Brown grafts, bone grafts, brephoplastic grafts, cutis grafts, delayed grafts, dermic grafts, epidermic grafts, fascia grafts, full thickness grafts, heterologous grafts, xenografts, homologous8123-112369-02 05552grafts, hyperplastic grafts, lamellar grafts, mesh grafts, mucosal grafts, Ollier-Thiersch grafts, omenpal grafts, patch grafts, pedicle grafts, penetrating grafts, split skin grafts, and thick split grafts. The methods include administering to the subject with the graft an effective amount of a chemokine cocktail composition, as disclosed herein, thereby increasing the adherence and acceptance of the graft. Methods are also provided to treat blisters and burns due to abrasion or chemical injury. These methods include the treatment of the skin or internal organs. These methods include treatment of ovary injury, for example, due to treatment with chemotherapeutics or treatment with cyclophosphamide; radiation- or chemotherapy-induced cystitis; or high-dose chemotherapy-induced intestinal injury. The methods include administering to the subject an effective amount of a chemokine cocktail composition, as disclosed herein, to promote healing of the blisters or burns. In some aspects of the disclosed methods, the subject is human. In some examples, the human subject exhibits impaired wound healing. In other examples, the human subject has a wound but is otherwise healthy. VI. Compositions and Administration In some aspects of the disclosed methods, the chemokine cocktail is formulated for topical, intranasal, inhalation, intravenous, intramuscular, intradermal, or subcutaneous administration. The chemokine cocktails can be administered ex vivo (such as to a cell) or in vivo to a subject. Generally, it is desirable to prepare the compositions as pharmaceutical compositions appropriate for the intended application. Accordingly, methods for making a medicament or pharmaceutical composition containing the chemokine cocktail are included herein. Typically, preparation of a pharmaceutical composition (medicament) entails preparing a pharmaceutical composition that is essentially free of pyrogens, as well as any other impurities that could be harmful to humans or animals. Typically, the pharmaceutical composition contains appropriate salts and buffers to render the components of the composition stable and allow for uptake of the chemokine proteins by target cells. Therapeutic compositions can be provided as parenteral compositions, such as for injection or infusion. Such compositions are formulated generally by mixing a disclosed chemokine / chemokine cocktail at the desired degree of purity, in a unit dosage injectable form (solution, suspension, or emulsion), with a pharmaceutically acceptable carrier, for example one that is non-toxic to recipients at the dosages and concentrations employed and is compatible with other ingredients of the formulation. In addition, a disclosed chemokine cocktail can be suspended in an aqueous carrier, for example, in an isotonic buffer solution at a pH of about 3.0 to about 8.0, such as at a pH of about 3.5 to about 7.4, 3.5 to 6.0, or 3.5 to about 5.0. Useful buffers include sodium citrate-citric acid and sodium phosphate-phosphoric acid, and sodium acetate / acetic acid buffers. The active ingredients,8123-112369-02 05552optionally together with excipients, can also be in the form of a lyophilisate and can be made into a solution prior to parenteral administration by the addition of suitable solvents. Solutions such as those that are used, for example, for parenteral administration can also be used as infusion solutions. Pharmaceutical compositions can include an effective amount of chemokines, or dispersed (for example, dissolved or suspended) in a pharmaceutically acceptable carrier or excipient. Pharmaceutically acceptable carriers and / or pharmaceutically acceptable excipients are known in the art and are described, for example, in Remington: The Science and Practice of Pharmacy, 23nded., London, UK: Academic Press, 2020. The nature of the carrier will depend on the particular mode of administration being employed. For example, parenteral formulations usually contain injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water, physiological saline, balanced salt solutions, aqueous dextrose, glycerol or the like as a vehicle. For solid compositions (such as powder, pill, tablet, or capsule forms), conventional non-toxic solid carriers can include, for example, pharmaceutical grades of mannitol, lactose, starch or magnesium stearate. In addition, pharmaceutical compositions to be administered can contain minor amounts of non-toxic auxiliary substances, such as wetting or emulsifying agents, preservatives, and pH buffering agents and the like, for example sodium acetate or sorbitan monolaurate. As used herein, “pharmaceutically acceptable carrier” includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the pharmaceutical compositions is contemplated. Supplementary active ingredients also can be incorporated into the compositions. For example, certain pharmaceutical compositions can include the chemokine cocktails in water, mixed with a suitable surfactant, such as hydroxypropylcellulose. Dispersions also can be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. The dosage form of the pharmaceutical composition will be determined by the mode of administration chosen. For instance, in addition to injectable fluids, topical and oral formulations can be employed. Oral formulations may be liquid (e.g., syrups, solutions, or suspensions), or solid (e.g., powders, pills, tablets, or capsules). For solid compositions, conventional non-toxic solid carriers can include pharmaceutical grades of mannitol, lactose, starch, or magnesium stearate. Actual methods of preparing such dosage forms are known, or will be apparent, to those of ordinary skill in the art. Implants can also be employed. The compositions that include a chemokine cocktail can be formulated in unit dosage form, suitable for individual administration of precise dosages. The amount of active compound(s)8123-112369-02 05552administered will be dependent on the subject being treated, the severity of the affliction, and the manner of administration, and is best left to the judgment of the prescribing clinician. Within these bounds, the formulation to be administered will contain a quantity of the active component(s) in amounts effective to achieve the desired effect in the subject being treated. The chemokine cocktail can be included in an inert matrix for either topical application or injection. As one example of an inert matrix, liposomes may be prepared from dipalmitoyl phosphatidylcholine (DPPC), such as egg phosphatidylcholine (PC). Liposomes, including cationic and anionic liposomes, can be made using standard procedures as known to one skilled in the art. Liposomes including chemokine cocktail can be applied topically or can be injected for systemic administration. In some formulations, the chemokine cocktail is slowly released over time as the liposome capsule degrades. These formulations, and others, provide advantages of a slow release drug delivery system, allowing the subject to be exposed to a substantially constant concentration. In one example, the chemokine cocktail can be dissolved in an organic solvent such as DMSO or alcohol as previously described and contain a polyanhydride, poly(glycolic) acid, poly(lactic) acid, or polycaprolactone polymer. For treatment of the skin, an effective amount (or a therapeutically effective amount) of a composition, as disclosed herein can be systemically or locally administered. In some aspects, the composition can be locally administered to the affected area of the skin, such as in the form of an ointment. In one aspect, the ointment is an entirely homogenous semi-solid external agent with a firmness appropriate for easy application to the skin. Such an ointment can include fats, fatty oils, lanoline, Vaseline, paraffin, wax, hard ointments, resins, plastics, glycols, higher alcohols, glycerol, water or emulsifier and a suspending agent. Using these ingredients as a base, a decoy compound can be evenly mixed. Depending on the base, the mixture can be in the form of an oleaginous ointment, an emulsified ointment, or a water-soluble ointment; oleaginous ointments use bases such as plant and animal oils and fats, wax, VASELINE and liquid paraffin. Emulsified ointments are comprised of an oleaginous substance and water, emulsified with an emulsifier. They can take either an oil-in-water form (O / W) or a water-in-oil-form (W / O). The oil-in-water form (O / W) can be a hydrophilic ointment. The water-in-oil form (W / O) initially lacks an aqueous phase and can include hydrophilic VASELINE and purified lanoline, or it can contain a water-absorption ointment (including an aqueous phase) and hydrated lanoline. A water-soluble ointment can contain a completely water- soluble Macrogol base as its main ingredient. Pharmaceutically acceptable carriers include a petroleum jelly, such as VASELINE, wherein the petroleum jelly contains 5% stearyl alcohol, or petroleum jelly alone, or petroleum jelly containing liquid paraffin. Such carriers enable pharmaceutical compositions to be prescribed in forms appropriate for consumption, such as tablets, pills, sugar-coated agents, capsules, liquid preparations, gels, ointments, syrups, slurries, and suspensions. When locally administered into cells8123-112369-02 05552in an affected area or a tissue of interest, the composition can be administered in a composition that contains a synthetic or natural hydrophilic polymer as the carrier. Examples of such polymers include hydroxypropyl cellulose and polyethylene glycol. A composition can be mixed with a hydrophilic polymer in an appropriate solvent. The solvent is then removed by methods such as air-drying, and the remainder is then shaped into a desired form (for example, a sheet) and applied to the target site. Formulations containing such hydrophilic polymers keep well as they have a low water-content. At the time of use, they absorb water, becoming gels that also store well. In the case of sheets, the firmness can be adjusted by mixing a polyhydric alcohol with a hydrophilic polymer similar to those above, such as cellulose, starch and its derivatives, or synthetic polymeric compounds. Hydrophilic sheets thus formed can be used. A therapeutically effective amount of a composition, as disclosed herein, can also be incorporated into bandages and dressings for wounds. VII. Overview of Aspects Aspect 1. A method of treating or inhibiting fibrosis in a subject, comprising administering to the subject an effective amount of a chemokine cocktail comprising: two or more of a CXCL4 protein, a CXCL9 protein, a CXCL10 protein, and a CXCL11 protein, or biologically active fragments or variants thereof; two or more of a CXCL4 protein, a CXCL9 protein, a CXCL10 protein, a CXCL11 protein and a CXCL12 protein, or biologically active fragments or variants thereof; or a CXCL1 protein and a CXCL8 protein, or biologically active fragments or variants thereof. Aspect 2. The method of aspect 1, wherein the CXCL1, CXCL4, CXCL8, CXCL9, CXCL10, CXCL11, and / or CXCL12 proteins are human proteins. Aspect 3. The method of aspect 1 or aspect 2, wherein the CXCL1, CXCL4, CXCL8, CXCL9, CXCL10, CXCL11, and / or CXCL12 protein comprises at least one chemical modification. Aspect 4. The method of any one of aspects 1-3, wherein: the amino acid sequence of the CXCL1 protein is at least 95% identical to SEQ ID NO: 1; the amino acid sequence of the CXCL4 protein is at least 95% identical to SEQ ID NO: 2; the amino acid sequence of the CXCL8 protein is at least 95% identical to SEQ ID NO: 3; the amino acid sequence of the CXCL9 protein is at least 95% identical to SEQ ID NO: 4; the amino acid sequence of the CXCL10 protein is at least 95% identical to SEQ ID NO: 5; the amino acid sequence of the CXCL11 protein is at least 95% identical to SEQ ID NO: 6; and / or the amino acid sequence of the CXCL12 protein is at least 95% identical to SEQ ID NO: 7.8123-112369-02 05552Aspect 5. The method of any one of aspects 1-4, wherein: the amino acid sequence of the CXCL1 protein comprises or consists of SEQ ID NO: 1; the amino acid sequence of the CXCL4 protein comprises or consists of SEQ ID NO: 2; the amino acid sequence of the CXCL8 protein comprises or consists of SEQ ID NO: 3; the amino acid sequence of the CXCL9 protein comprises or consists of SEQ ID NO: 4; the amino acid sequence of the CXCL10 protein comprises or consists of SEQ ID NO: 5; the amino acid sequence of the CXCL11 protein comprises or consists of SEQ ID NO: 6; and / or the amino acid sequence of the CXCL12 protein comprises or consists of SEQ ID NO: 7. Aspect 6. The method of any one of aspects 1-5, wherein the chemokine cocktail comprises two or more of: a CXCL4 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 6. Aspect 7. The method of aspect 6, wherein the chemokine cocktail comprises or consists of: a CXCL4 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 6. Aspect 8. The method of any one of aspects 1-5, wherein the chemokine cocktail comprises two or more of: a CXCL4 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 6.8123-112369-02 05552Aspect 9. The method of aspect 8, wherein the chemokine cocktail comprises or consists of: a CXCL4 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 6. Aspect 10. The method of any one of aspects 1-5, wherein the chemokine cocktail comprises two or more of: a CXCL4 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 6; and a CXCL12 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 7. Aspect 11. The method of aspect 10, wherein the chemokine cocktail comprises or consists of: a CXCL4 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 6; and a CXCL12 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 7. Aspect 12. The method of any one of aspects 1-5, wherein the chemokine cocktail comprises two or more of: a CXCL4 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 6; and8123-112369-02 05552a CXCL12 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 7. Aspect 13. The method of aspect 2, wherein the chemokine cocktail comprises or consists of: a CXCL4 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 6; and a CXCL12 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 7. Aspect 14. The method of any one of aspects 1-5, wherein the chemokine cocktail comprises: a CXCL1 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 1; and a CXCL8 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 3. Aspect 15. The method of aspect 14, wherein the chemokine cocktail comprises or consists of: a CXCL1 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 1; and a CXCL8 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 3. Aspect 16. The method of any one of aspects 1-11, wherein the fibrosis is fibrosis of the skin, lung, heart, kidney or liver. Aspect 17. The method of any one of aspects 1-12, wherein the subject is human. Aspect 18. A method for increasing extracellular matrix (ECM) production and / or treating a wound in a subject, comprising administering to the subject an effective amount of a chemokine cocktail comprising: a CXCL1 protein and a CXCL8 protein, or biologically active fragments or variants thereof; or8123-112369-02 05552a CXCL1 protein, a CXCL8 protein, and a CCL2 protein, or biologically active fragments or variants thereof. Aspect 19. The method of aspect 18, wherein the CXCL1, CXCL8 and / or CCL2 proteins are human proteins. Aspect 20. The method of aspect 18 or aspect 19, wherein the CXCL1, CXCL8 and / or CCL2 protein comprises at least one chemical modification. Aspect 21. The method of any one of aspects 18-20, wherein: the amino acid sequence of the CXCL1 protein is at least 95% identical to SEQ ID NO: 1; the amino acid sequence of the CXCL8 protein is at least 95% identical to SEQ ID NO: 3; and / or the amino acid sequence of the CCL2 protein is at least 95% identical to SEQ ID NO: 8. Aspect 22. The method of any one of aspects 18-21, wherein: the amino acid sequence of the CXCL1 protein comprises or consists of SEQ ID NO: 1; the amino acid sequence of the CXCL8 protein comprises or consists of SEQ ID NO: 3; and / or the amino acid sequence of the CCL2 protein comprises or consists of SEQ ID NO: 8. Aspect 23. The method of any one of aspects 18-22, wherein the subject is human. Aspect 24. The method of any one of aspects 1-23, wherein the chemokine cocktail is formulated for topical, intranasal, inhalation, intravenous, intramuscular, intradermal, or subcutaneous administration. EXAMPLES The following examples are provided to illustrate particular features of certain aspects of the disclosure, but the scope of the claims should not be limited to those features exemplified. Example 1: Materials and Methods Maintenance and treatment of cells Primary human dermal fibroblasts, as described previously (Yasuoka et al., Arthritis Rheum 2006, 54:3001-10; Brissett et al., Arthritis Rheum 2012, 64:272-80), were used for all experiments with passage numbers kept low (≤ 6) with no in vitro aging effects noted. Acquisition of these human8123-112369-02 05552cells have been classified by the University of Pittsburgh Institutional Review Board as exemption 4e and, therefore, do not qualify as human-subject research by National Institutes of Health (NIH) guidelines. Cells were obtained from human donors in adherence with IRB Protocol ID: STUDY20050297. Cells were maintained in a complete medium containing DMEM with GLUTAMAX (Thermo Fisher Scientific, 10566016) with 10% FBS and antibiotics. Cells were cultured in a quiescent medium containing DMEM, 0.5% dialyzed FBS, and antibiotics for 16 hours prior to beginning the treatment protocol and throughout treatment. Fibroblasts were treated with human recombinant TGF-β (10 ng / mL) (R&D Systems, 240-B-002) to induce an activated fibroblast phenotype for 24 hours or were left unstimulated. Then, the following concentrations of chemokines were added to cells either alone or in cocktails for 24 hours: 100 ng / mL CXCL4 (Peprotech, 300-16- A), 10 ng / mL CXCL9 (Peprotech, 300-26-A), 100 ng / mL CXCL10 (Peprotech, 300-12-A), 25 ng / mL CXCL11 (Peprotech, 300-46-A), 10 ng / mL CXCL12 (Peprotech, 300-28A-A), 10 ng / mL CXCL1 (Peprotech, 300-11-A), 10 ng / mL CXCL8 (Peprotech, 200-08M-A), 10 ng / mL CCL2 (Peprotech, 300-04-A). Cocktail combinations are outlined in Table 1 and were designed according to structure and receptor ligand pairing, as described in Table 2. RNA Extraction and Real-time qRT-PCR Dermal fibroblasts were cultured for 48 hours, seeded in 8 well chamber slides, then stimulated with TGF-β for 24 hours before receiving chemokine treatments, as described above, with two technical replicates and cells receiving no treatment as a negative control. Following treatments, total RNA was extracted from cells using the RNeasy Mini Kit (Qiagen, 74104). RNA was treated with DNase1 during extraction, according to the manufacturer’s instructions (Qiagen, 79254). RNA was quantified on a NanoDrop instrument. A portion of RNA was reserved for RNA Sequencing, while the remaining RNA was converted to cDNA for quantitative real time polymerase chain reaction (qRT-PCR) using the Clontech EcoDry Premix (Double Primed) kit (Takara, 639548). Primers for COL1A1, TNC, FN1, ACTA2, and DCN were designed using a combination of PrimerQuest Software (Integrated DNA Technologies) and the NCBI Primer Blast tool and are displayed in Table 3. A mixture of cDNA, gene-specific primers (Integrated DNA Technologies), and PowerUp Sybr Green Master Mix (Invitrogen, A25742) was used to assess mRNA expression using an Applied Biosystems 7900HT instrument. Amplification curves and melt curves were visualized in Applied Biosystems software for quality control. The delta, delta Ct method was used to determine expression of each gene relative to GAPDH. Relative expression was then normalized to that of the control group.8123-112369-02 05552RNA Sequencing Samples were analyzed by NanoDrop for RNA purity (OD260 / OD280), by agarose gel electrophoresis for RNA integrity and potential contamination, and by Agilent 2100 to verify RNA integrity. For library preparation, mRNA was purified from total RNA using poly-T oligo-attached magnetic beads through the removal of rRNA by NEBNEXT ULTRA RNA Library Prep Kit (NEB #E7530). Library quality assessment was assured by diluting the library to 1.5 ng / μL by the preliminary quantitative result by Qubit2.0 and detecting the insert size by Agilent 2100. The library effective concentration (> 2nM) was quantified by qRT-PCR, to ensure the library quality. To avoid low quality reads or reads with adaptors, raw reads were filtered. Raw reads filtering included removing reads containing adaptors, removing reads containing N > 10% (N represents bases that could not be determined), and removing reads with a Qscore (Quality value) of over 50% bases of the read is <= 5. Sequencing was performed using an Illumina Platform PE150 and quantified by HTSeq (v0.6.1) using the union mode, with an average coverage of 50 million raw reads and 47 million clean reads per sample. Reads per kilobase of exon model per million mapped reads (FPKM) was then calculated. Paired-end reads were aligned to the hg19 human reference genome using STAR aligner (v2.5) at mismatch:2. Approximately 88.30% of all reads aligned uniquely to the reference genome. Prior to differential gene expression analysis, the read counts were adjusted using the R program edgeR (3.16.5) through one scaling normalized factor. The p-values were adjusted using the Benjamini & Hochberg (BH) correction. Corrected p-values of < 0.05 and absolute fold change of > 1 were set as the threshold for significantly differential expression. Differential expression analysis Prior to differential gene expression analysis, for each sequenced library, the read counts were adjusted by edgeR program package (v3.16.5) through one scaling normalized factor. Differential expression analysis of two conditions was performed using the edgeR R package. The p-values were adjusted using the Benjamini & Hochberg method to control for False Discovery Rate (FDR). Genes with an adjusted p-value < 0.05 and [log2(Fold Change)] > 1 found by EgdeR were assigned as differentially expressed. The Venn diagrams were prepared using the function vennDiagram in R and were based on the gene list for different treatment groups. GO, KEGG, and Reactome enrichment analyses of differentially expressed genes Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome enrichment analyses of differentially expressed genes were implemented by the ClusterProfiler R package (v2.4.3), in which gene length bias was corrected. Terms with corrected p-values < 0.05 were considered significantly enriched by differentially expressed genes.8123-112369-02 05552Immunofluorescent Staining Human dermal fibroblasts of passage ≤ 6 were seeded in 8 well chamber slides (Thermo- Scientific 154534) at 3.0 x 103 cells / well and were cultured in a 5% CO2 atmosphere, at 37°C in DMEM medium (Corning 10-013 CM) containing normal glucose (4.5 g / L), 10% fetal calf serum, 1% pen / strep (Gibco 25030-081) and 1% L-glutamate (Gibco 15240-062). Once 80% confluent, cells were treated as described above. After 24 hours, cells were washed with 1X PBS (Gibco 14190-144) and fixed with 4% PFA (EMS 157-4). Cells were permeabilized using 0.1% Triton (Sigma Life Science T9284) in 1X PBS before staining. Cells were washed and blocked with 1% BSA (Fisher BioReagents 9048-46-8) for 30 minutes at 37°C in a humid chamber. Cells were incubated with primary antibody; LOX (1:100, Abcam ab31238), fibronectin (1:250, Abcam ab2413), decorin (1:00, Abcam ab54728), or p-SMAD2 (1:200, Abcam ab53100) in PBS buffer (1% BSA) overnight at 4°C. After 24 hours, cells were washed with PBS-Tween20 (Sigma-Aldrich P7949). Cells were then incubated with Alexa Fluor 488 conjugated goat anti-rabbit (Abcam ab150077) or goat anti-mouse (Abcam ab150113) secondary antibody at a (1:250) dilution in 1% BSA for 30 minutes at 20°C. Lastly, cells were counterstained with DAPI (Vector Laboratories H-1200). Cells were imaged with a XX confocal microscope at XX. Fluorescence was quantified by ImageJ image analysis software (v. 1.52g National Institutes of Health software) and mean fluorescence intensity (MFI) was calculated. Statistics For quantitative measurements, results are presented as mean ± standard error. ANOVA and Student’s T-tests were performed in GraphPad Prism software (Version 9.0.0). P-values < 0.05 were considered statistically significant. For RNA sequencing, multiple hypothesis testing was used to adjust p-values. For qRT-PCR, the ROUT method with Q = 1% was used to identify outliers in data for each gene, which were eliminated from graphs and statistical testing. Example 2: Design of chemokine panels and cocktails Recent literature demonstrates the role of C-X-C and C-C chemokines in fibrosis. The present studies examined the individual and synergistic effects of chemokines CXCL4, CXCL9, CXCL10, CXCL11, CXCL12, CXCL1, CXCL8, and CCL2 on fibroblast ECM transcription, secretion, and organization via RT-qPCR, immunofluorescence, and RNA Seq Analysis (FIG.13). Three chemokine cocktails were developed based on their ELR sequence (ELR+ vs. ELR-) and function (pro- angiogenic vs. anti-angiogenic) and known ligand-receptor pairing (Table 1). The custom designed cocktails included Cocktail 1 (C1), which was composed of ELR- chemokines that bind the CXCR3 receptor (CXCL4, CXCL9, CXCL10, and CXCL11). Cocktail C2 included all chemokines in C1 along with the ELR-, but pro-angiogenic chemokine CXCL12. C3 was a combination of CXCL1,8123-112369-02 05552CXCL8, and CCL2. C4 was a cocktail of the ELR+ plus pro-angiogenic chemokines CXCL1 and CXCL8. Example 3: ELR+, but not ELR-, chemokine treatments reduce fibroblast production of structural proteins and matrix molecules Immunofluorescent staining and qRT-PCR were used to evaluate the impact of chemokines and chemokine cocktails on the expression of ECM-related molecules in dermal fibroblasts from healthy human patients. The effects of angiostatic chemokines were evaluated by CXCL4, CXCL9, CXCL10, CXCL11, and the ELR- pro-angiogenic chemokine, CXCL12 on fibroblast transcription of the profibrotic ECM mRNA COL1A1, FN1, TNC; ACTA2, a marker of fibroblast activation; and DCN, an anti-fibrotic matrikine. These chemokine treatments rendered no effect on mRNA levels of matrix proteins TNC and COL1A1, structural protein ACTA2, or anti-fibrotic matrikine DCN (FIG. 1). However, fibroblast stimulation with CXCL4 alone upregulated mRNA expression of FN1 (p < 0.5) (FIG.1). Next, studies were performed on the impact of known angiogenic chemokines on fibroblast matrix production, alone or in cocktails. Treatment with CXCL1 (p < 0.05), CXCL8 (p < 0.0001), CCL2 (p < 0.01), or C4 (CXCL1 and CXCL8) (p < 0.001) suppressed mRNA expression of TNC (FIG.2) but had no significant impact on COL1A1 or FN1 expression. All ELR+ chemokine treatments inhibited fibroblast expression of ACTA2, with CXCL8 and C4 (CXCL8 and CXCL1) (p < 0.0001) causing the greatest reduction (FIG.2). CXCL8 treatment alone reduced DCN expression (p < 0.05) compared to vehicle-treated cells, although ELR+ cocktails had little impact on fibroblast DCN expression (FIG.2). Example 4: ELR- chemokine stimulation is unable to rescue TGF-β-mediated inhibition of DCN mRNA expression in activated dermal fibroblasts ELR- CXCR3 ligand chemokines and, in some cases, CXCL12, can inhibit fibrosis in vivo. Therefore, further studies evaluated how chemokines impacted transcriptional responses to TGF-β in dermal fibroblasts. ACTA2, TNC, COL1A1, DCN, and FN1 are all known targets of canonical TGF- β signaling. Cells were pre-treated with TGF-β for 24 hours and either incubated with TGF-β alone or TGF-β and individual chemokines or chemokine cocktails. Compared to cells receiving no treatment, cells stimulated with TGF-β for 24 hours showed a robust induction in the expression of known downstream transcriptional targets TNC (p < 0.001), COL1A1 (p < 0.0001), and FN1 (p <0.001) (FIG.3) as expected. Treatment with CXCL4 (p < 0.01), CXCL9 (p < 0.001), CXCL10 (p < 0.001), CXCL11 (p < 0.05), CXCL12 (p < 0.001), and the C2 cocktail (p < 0.05) significantly reduced TGF- β-mediated induction in TNC expression (FIG.3). The C1 cocktail had a similar, but not statistically significant effect (FIG.4A). Treatment with these ELR- peptides and cocktails also tended to reduce8123-112369-02 05552TGF-β-induced COL1A1 and FN1 (FIG.3) expression, a trend that reached statistical significance with application of the C1 cocktail and COL1A1 expression (p < 0.05) (FIG.3). ACTA2 expression was not significantly altered by TGF-β or ELR- chemokine or chemokine cocktail treatment by the 24-hour timepoint (FIG.3). On the other hand, none of the ELR- chemokines or chemokine cocktails were able to rescue TGF-β-mediated inhibition of DCN mRNA expression (FIG.3). Example 5: ELR+ chemokine CXCL8 inhibits TGF-β upregulation of TNC expression in activated fibroblasts There were expectations that angiogenic chemokines and cocktails may potentiate the effects of TGF-β on ECM target genes. The results demonstrated that treatment with CXCL8 significantly inhibited TGF-β upregulation of TNC expression (p < 0.01) (FIG.4). Similarly, treatment with CXCL1 (p < 0.05), CXCL8 (p < 0.01), CCL2 (p < 0.01), and cocktail C4 (p < 0.05) inhibited TGF-β- mediated upregulation of COL1A1 (FIG.4). The C4 cocktail stimulation of activated fibroblasts significantly inhibited the expression of ACTA2 at the 24-hour timepoint (FIG.4). No significant effects were found from these chemokines or cocktails on TGF-β increased expression of FN1 (FIG. 4) or decreased expression of DCN (FIG.4). Next, results showed the inverse effects of TGF-β on fibronectin (FIGS.7A-7D) and the anti- fibrotic ECM protein decorin (FIGS.6A-6D) vs. the ECM protein fibronectin (FIGS.7A-7D), the pro-fibrotic enzyme lysyl oxidase LOX (FIGS.5A-5D) which cross-links collagen, and pSMAD (FIGS.8A-8D), a mediator of downstream TGF-β signaling. The effects of chemokines cocktail on TGF-β-mediated upregulation of fibronectin, decorin, LOX, and pSMAD2 was quantified by immunofluorescent staining. Distinctively, fibronectin is increased independently of TGF-β with stimulation of cells with the C3 cocktail (p < 0.01) (FIGS.7A, 7C). Fibroblasts displayed increased fibronectin levels with CXCL8 stimulation alone (p < 0.0001) or with the C3 cocktail (p < 0.0001) (FIGS.7A, 7C). However, the CXCL1 + CCL2 or cocktail 4 (C4) were insufficient to increase fibronectin expression significantly beyond that of TGF-β alone (FIGS.7A, 7C). Additionally, CXCL1 (p < 0.05), CCL2 (p < 0.0001), CXCL8 (p < 0.0001), and the C3 cocktail (CXCL1 + CXCL8 + CCL2) (p < 0.05) increased decorin levels in TGF-β-activated fibroblasts (FIGS.6B, 6D). These results mark a unique stimulatory role for CXCL8 in fibroblast pro-fibrotic and anti-fibrotic ECM production independently of TGF-β. Data shows consistent LOX pathway activation with CXCL8 treatment in both quiescent and TGF-β-activated fibroblasts (p < 0.0001) (FIGS.5A, 5C). The CXCL1 and CCL2 cocktail (p < 0.01) increased LOX levels independently of TGF-β (FIGS.5A, 5C). Uniquely in TGF-β activated fibroblasts, LOX expression increased with CCL2 alone (p < 0.0001) or the synergy of CXCL1 + CCL2 (p < 0.05) (FIGS.5A, 5C).8123-112369-02 05552The last target downstream of signaling TGF-β was pSMAD2 (FIGS.8B, 8D). pSMAD2 displayed a counter regulatory signal pattern downstream of TGF-β. Findings show that CCL2 (p < 0.0001) and CXCL8 (p < 0.0001) alone increase pSMAD2 independently of TGF-β (FIGS.8B, 8D). Interestingly, CXCL1 / CCL2 synergistically inhibited pSMAD2 expression compared to controls (p < 0.05) (FIGS.8B, 8D). CXCL1 (p < 0.05), CCL2 (p < 0.0001), and CXCL8 (p < 0.0001) increased pSMAD2 levels in TGF-β activated fibroblasts compared to TGF-β treatment alone. The C3 chemokine cocktail of CXCL1 + CXCL8 + CCL2 also increased pSMAD2 levels in TGF-β activated fibroblasts (p < 0.05), albeit not as high as CXCL1 or CXCL8 alone (FIGS.8B, 8D). Example 6: RNA-Sequence identified gene enrichment between TGF-β and CXCL8 in collagen formation / biosynthesis and ECM organization RNA sequence studies were focused on CXCL8 and ELR+ chemokine cocktails to further explore their unique relationship and significant effects on TGF-β signaling and ECM regulation and production in fibroblasts. Bulk RNA-sequencing and differential gene expression analysis revealed strong cluster expression of CXCL8 + TGF-β related to the prominent ELR+ moderators in CXCL1 and CCL2 as well as the synergy with these chemokine cocktails in TGF-β-activated fibroblasts (FIG. 9A). Venn diagrams in FIG.9B show a higher interpopulation of gene expression (1,948 shared genes) in TGF-β stimulated clusters with CXCL8-stimulated cells displaying moderately higher overlap (1,869 shared genes) with all C4 (CXCL1 + CXCL8) + TGF-β related clusters compared to TGF-β controls (FIG.9B). Together, results in FIG.9C show a higher degree of upregulated genes in CXCL8 + TGF-β > TGF-β controls > C4 + TGF-β (FIG.9C). However, from the number of DEGs, C4 + TGF-β cluster analysis had the least number of DEGs (n = 2255), specifically compared to controls and CXCL8 + TGF-β stimulated cells (n = 2348) (FIG.9C). Further evaluation of CXCL8 + TGF-β RNA Seq analysis by Gene Ontology (GO) enrichment in shows a conditional increase in ECM / collagen activity (FIG.10A). The most prominent results were evidenced in regulation of genes related to ECM matrix organization and extracellular structure organization (n = 101 padj = 2.73x10-15) (FIG.10A). Collagen metabolic processes (n = 42, padj = 9.10x10-9) were also among the most differentially regulated terms compared to the control (FIG.10A), which parallels the previous observations of CXCL8 regulation of fibroblast matrix production. KEGG analysis found the top 6 most highly differentially altered pathways between the CXCL8 + TGF-β stimulated cells and the control group to be associated with focal adhesion (n=56, padj = 2.46x10-5), pathways in cancer (n=73, padj = 0.0008907), protein processes in the endoplasmic reticulum (n=44, padj = 0.0008907), ECM-receptor interaction (n=27, padj = 0.0010903), regulation of the actin cytoskeleton (n=50, padj = 0.003267), and TGF-β signaling (n=24, padj = 0.0129294) (FIG.10B). The CXCL8 + TGF-β treatment group significantly affected protein8123-112369-02 05552digestion and absorption (n = 22, padj = 0.0011173) (FIG.10B). This was not seen amongst the CXCL1 + TGF-β or C4 + TGF-β treatment groups, suggesting a unique response for CXCL8 in these processes, possibly affecting tissue remodeling. CXCL8 + TGF-β vs. TGF-β stimulation alone showed a stark difference in pathways associated with metabolic regulation (FIG.10B). Next, studies were directed to understand pathway analyses with a greater look at the biological implications of these chemokine cocktails through a Reactome enrichment analysis for insight into the effect of CXCL8 and TGF-β stimulation of fibroblasts alone (FIG.10C). ELR+ chemokines, individually or in the C4 chemokine cocktail, (CXCL1 + CXCL8), differentially regulated fibroblast ECM production and cell / matrix interactions. Opposed to C4 + TGF-β vs. control, CXCL8 + TGF-β vs. control differentially regulated a greater number of genes associated with ECM organization (92 vs.83), collagen formation (36 vs.27), collagen biosynthesis and modifying enzymes (29 vs.22), assembly of collagen (24 vs.19), and elastic fiber formation (20 vs.17) (FIG. 10C). CXCL8 + TGF-β vs. control and also significantly regulated pathways associated with the degradation of ECM (39 vs.34) opposed to C4 + TGF-β vs. control (FIG.10C). Studies looked further at how C4 ELR+ chemokine cocktail modulated the most enriched term from Reactome enrichment analysis, extracellular matrix organization. FIG.11 displays the log2 fold change of all genes within the Reactome term of ECM organization. The C4 ELR+ chemokine cocktail (CXCL1 + CXCL8) + TGF-β resulted in a negative log2 fold change for COL1A1 compared to that of each chemokine singularly with TGF-β. Interestingly, this was also seen with the anti- fibrotic matrikine, DCN, with the C4 + TGF-β treatments downregulating DCN expression while CXCL1 + TGF-β and CXCL8 + TGF-β upregulated DCN expression (FIG.11) compared to the control group. ELR+ chemokines had little effect on TGFβ2, but upregulated TGFβ1 expression compared to TGF-β alone (FIG.11). Finally, to increase the translational component of these studies, primary human dermal fibroblasts from SSc patients were studied. These cells were subject to the same chemokine / chemokine cocktail treatments as described in the studies above. Interestingly, fibroblasts derived from patients with a low modified Rodnan’s Skin Score (mRSS: 12, 17), responded very differently to chemokine treatment compared to fibroblasts from patients with a high disease severity (mRSS: 34, 43). CXCL8 upregulated both FN1 and DCN in low mRSS fibroblasts (p<0.05) (FIG. 12). Conversely, CXCL4 and the ELR- chemokine cocktails elevated FN1 and DCN expression in cells derived from high mRSS individuals (FIG.12). Of note, Cocktail 1 (CL4, CXCL9, CXCL10, CXCL11) increased levels of the fibronectin, while Cocktail 2, (CL4, CXCL9, CXCL10, CXCL11, CXCL12) increased expression of the anti-fibrotic matrikine DCN.8123-112369-02 05552Discussion Advancement of chemokine / cytokine therapies to treat fibrosis is in high demand. Multiple pathogenic factors involved in inflammation and fibrosis justify the need to advance the use of chemokine cocktail inhibition in clinical trials. Current advances in immunotherapies have made it suitable for advanced therapeutic incorporation of chemokine / cytokine cocktail inhibitors (Mailliard et al., Cancer Res 2004, 64:5934-7). Even though some of these studies show promising early data, establishing the ideal inhibitory chemokine / cytokine cocktails to use and their mechanisms of action are in the early stage of development (Castiello et al., Mol Ther 2013, 21:476-84). Most of the advances in this field are seen in cancer, where combination therapies to eradicate tumor growth are implemented to target dendritic cells (Garofano et al., Int J Mol Sci 2019, 20; Lee et al., Vaccine 2002, 20 Suppl 4:A8-A22). Current studies in chemokine therapeutics fail to translate to the clinic, likely due to chemokine synergy in the complex wound healing environment. However, targeting the pathogenesis of wound healing and chronic inflammation presents an urgent unmet clinical need. These efforts need to be mechanistically described. The understanding of the role of chemokines is key in the fibrotic process and their modulation of fibroblast behavior, as fibroblasts are the primary producers of ECM. It is important to highlight that understanding the TGF-β-induced fibrotic response is difficult to dissect due to its heterogeneity and the feedback mechanisms by which ECM components and chemokine expression impact cellular processes. As some examples of this heterogeneity, fibronectin is known to induce expression of CXCL1 (Pulai et al., J Immunol 2005, 174:5781-8). Tenascin-C is known to increase expression of CCL2 (Catalan et al., J Clin Endocrinol Metab 2012, 97:E1880-9). Decorin induces expression of CXCL10 (Bocian et al., J Biol Chem 2013, 288:12699-711) and tenascin-C also positively regulates TGF-β signaling (Carey et al., Am J Physiol Lung Cell Mol Physiol 2010, 299:L785-93). Importantly, CXCL12 decreases FN1 expression in responses to TGF-β and high glucose (Zhang et al., Exp Cell Res 2013, 319:1796-803). Equally, TGF-β signaling can impact chemokine expression in major regulatory ways, as TGF-β negatively regulates expression of CXCL1 in fibroblasts (Fang et al., PLoS One 2015, 10:e0135063; Zou et al., BMC Cancer 2014, 14:781). Targeting of the TGF-β pathway by chemokines and cytokines in clinical trials, such as interleukin-1 (IL-1), is limited due to the potential safety concerns of collateral effects in vivo (Dinarello, Blood 2011, 117:3720-32). Additionally, in the vasculature, TGF-β can target chemokines in specific cellular subsets. For example, CCL2 is a direct target gene of TGF-β in endothelial cells (Ma et al., Blood 2007, 109:987-94) and enhances the migratory effects of TGF-β in these cells. Although TGF-β is a powerful stimulant of fibrosis, the reality of anti-fibrotic TGF-β-targeted agents needs to be further elucidated (Hinz, Exp Eye Res 2016, 142:56-70)71. Cytokines and growth factors including IL-1, tumor necrosis factor-alpha (TNF-α), TGF-β, platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) have been implicated as8123-112369-02 05552promoters of fibrotic phenotype (Bhattacharyya et al., Matrix Biol 2011, 30:235-42). Both canonical and non-canonical signaling activated by TGF-β can promote fibrosis through upregulation of ECM proteins (Meng et al., Nat Rev Nephrol 2016, 12:325-38), including collagen 1 alpha 1 (Jimenez et al., J Biol Chem 1994, 269:12684-91), tenascin-C (Ignotz and Massague, J Biol Chem 1986, 261:4337-45), and fibronectin 1 (Bhattacharyya et al., Nat Commun 2016, 7:11703). On the other hand, there is an antagonistic relationship between TGF-β signaling and expression of the anti-fibrotic ECM protein decorin (Yamaguchi et al., Nature 1990, 346:281-4; Mauviel et al., J Biol Chem 1995, 270:11692-700). It is important to discuss the distinct mechanisms by which TGF-β induces TNC, COL1A1, FN1 expression and reduces DCN. Previous studies have demonstrated the critical role of TGF-β-mediated upregulation of TNC in the development of lung fibrosis in mice (Carey et al., Am J Physiol Lung Cell Mol Physiol 2010, 299:L785-93). COL1A1 is activated by TGF-β responsive elements upstream of the transcriptional start site (Jimenez et al., J Biol Chem 1994, 269:12684-91) and through DNA methylation mechanisms (Pan et al., PLoS One 2013, 8:e60335). Importantly, SMAD4 is required for TGF-β-mediated upregulation of COL1A1, but not FN1 (Tsuchida et al., Kidney Int 2003, 63:2000-9). The complex layers of feedback directing fibroblast ECM production were described in our results. Studies helped determine the impact of chemokines and chemokine cocktails on the transcriptional response of dermal fibroblasts to TGF-β stimulation. Particularly, evaluation of gene transcripts and protein levels was performed on TNC, COL1A1, DCN, and FN1, targets of canonical TGF-β signaling. Table 1 shows the chemokine cocktails used for treatments, along with their respective receptors, outlined in Table 2. ELR- chemokines and their receptors have proven critical in the fate of wound healing. Mice with a global knockout of CXCR3, a receptor for CXCL9, CXCL10, and CXCL11 display reduced expression of laminin 5, collagen IV, and collagen VII in the basement membrane of the wound bed of full and partial-thickness excisional wounds, even 90 days post healing (Yates et al., Wound Repair Regen 2009, 17:34-41). Interestingly, while deletion of CXCL10 inhibits experimental liver fibrosis, systemic administration of CXCL10 reduces experimental pulmonary fibrosis and neutralizing antibody antagonizing the CXCR3-CXCL10 axis promotes renal fibrosis (Sahin and Wasmuth, Biochim Biophys Acta 2013, 1832:1041-8). It has been previously shown that CXCL11 reduces pulmonary collagen deposition, procollagen gene expression, ECM deposition and pathological fibrosis in a murine bleomycin-induced lung fibrosis model (Burdick et al., Am J Respir Crit Care Med 2005, 171:261-8). ELR- chemokines and chemokine cocktails did not significantly alter quiescent fibroblast transcription of matrix molecules of COL1A1, TNC, ACTA2, and DCN. This may suggest ELR- chemokine regulation of fibroblast matrix production specifically inhibits growth-factor-dependent pro-fibrotic signaling. This is supported by findings in which ELR- chemokines and chemokine cocktails significantly downregulated COL1A1 and TNC expression in TGF-β-activated, but not8123-112369-02 05552quiescent fibroblasts (FIG.2, FIG.4). On the other hand, CXCL12 and / or CXCR4 signaling has been shown to facilitate procollagen I secretion (Patalano et al., Sci Rep 2018, 8:3499), the expression of COL3A1 (Nassari et al., Sci Rep 2017, 7:17279), increased collagen deposition (Li et al., Exp Ther Med 2020, 19:1844-54), α-SMA expression (Kim et al., Invest Ophthalmol Vis Sci 2013, 54:7198- 206), and has been suggested as a means of autocrine upregulation of fibrotic pathologies (Li et al., Exp Ther Med 2020, 19:1844-54). However, previously reported data suggests CXCL12 / CXCR4 mediates α-SMA and collagen 1 is accomplished independently of TGFβ / TGFβR-induced SMAD signaling (Rodriguez-Nieves et al., PLoS One 2016, 11:e0159490). Interestingly, data shows no significant difference in COL1A1 expression in CXCL12 vs. CXCL12 + TGF-β treated cells. Rather, COL1a1 was significantly inhibited in TGF-β activated fibroblasts under stimulation of the C1 chemokine cocktail (CXCL4 + CXCL9 + CXCL10 + CXCL11 + CXCL12). This was not achieved by stimulation with any of these chemokines individually. These data suggest, CXCL12 may in fact have the opposite effect on COL1A1 expression of that proposed in the current literature when in combination with other ELR- chemokines. Moreover, CXCL4, CXCL9, CXCL10, CXCL12, and C2 (CXCL4 + CXCL9 + CXCL10 + CXCL11) all significantly reduced TNC in TGF-β activated fibroblasts compared to TGF-β alone (FIG.4). Others have shown that although CXCL10 was found to be the CXCR3 chemokine ligand primarily upregulated in the infarcted heart, knocking out CXCR3 did not affect collagen deposition, collagen remodeling, TGF-β signaling. CXCL10 did, however, inhibit basic fibroblast growth factor (bFGF)-induced cardiac fibroblast migration in a CXCR3-independent manner (Saxena et al., Cardiovasc Res 2014, 103:217-27). Hence, more work is needed to fully understand the anti-fibrotic role of CXCL10 in growth-factor induced fibroblast migration and ECM production. Results suggest a role for CXCL10 and ELR- chemokines in TGF-β-induced tenascin-C inhibition. Conversely, studies found the pro-angiogenic chemokines, notably CXCL1 and CXCL8, to more substantially regulate the TGF-β-induced ECM production of human dermal fibroblasts. Results also showed a decrease in TNC and COL1A1 with the ELR+ chemokine, CXCL8 (FIG.3A). However, there were contrasting results as what is reported in the literature that had shown CXCL8 has been reported to induce α-SMA and TNC signaling (Schauer et al., Urology 2008, 72:205-13) and that CXCL12, CXCL8, and CXCL5 treatment increased TGF-β1, COL1 and ACTA2 gene transcription, caused gel contraction, and induced myofibroblast phenoconversion independently of TGF-β (Gharaee-Kermani et al., PLoS One 2012, 7:e49278). Future studies will aim to explore different confounding variables that make such distinctions in dermal fibroblast activation pathways. On the other hand, stimulation with the ELR+ chemokine, CXCL1, suppressed the expression of TGF-β signaling components (FIG.3), just as TGF-β represses CXCL1 activity (Zou et al., BMC Cancer 2014, 14:781). This asserts the importance of further investigation to dissect this bi-directional8123-112369-02 05552act of repression to fully determine the effects of chemokines on TGF-β induced ECM production in vivo. Studies also provided insight on the potential interaction of TGF-β with ELR+ chemokines. Treatment with CXCL1 (p < 0.05), CXCL8 (p < 0.0001), CCL2 (p < 0.01), or C4 (CXCL1 and CXCL8) (p < 0.001) suppressed mRNA expression of TNC (FIG.3A). This is significant, as both CXCL8 and CCL2 have been described as biomarkers of fibrotic disease, such as in systemic sclerosis (SSc) or scleroderma (Hasegawa et al., Mod Rheumatol 2013, 23:1076-84), particularly in fibroblasts of an in vitro SSc model (Fineschi et al., Arthritis Rheum 2008, 58:3913-23). Moreover, the CCL2 receptor (CCR2) is thought to increase fibroblast responsiveness to TGF-β by increasing TGF-βR2 expression (Gharaee-Kermani et al., PLoS One 2012, 7:e49278). CCL2 / CCR2 signaling increases TGFβ1-induced fibronectin production (Park et al., Am J Physiol Renal Physiol 2008, 295:F749-57) in a TGF-β1 and downstream NF-κB-dependent manner (Giunti et al., Diabetologia 2008, 51:198-207), although the increase of FN1 mRNA by CCL2 has been contradicted (Yamamoto and Nishioka, J Invest Dermatol 2003, 121:510-6). CCL2 also increases DCN mRNA expression (Yamamoto and Nishioka, J Invest Dermatol 2003, 121:510-6), which aligns with the trend in the data obtained so far, although it did not reach statistical significance. Results showed decreased COL1A1 and FN1 production with CXCL8 stimulation (FIG.5A) which aligns with the differential gene expression enrichment analyses which found collagen / ECM related gene pathways to be differentially altered with CXCL8+ TGF-β vs. TGF-β stimulation alone (FIG.9). These findings contrast that of a previous study that found TGF-β1 + IL-6 + CXCL8 stimulation of fibroblasts increases COL1 expression, α-SMA positive cells, total collagen content, and FN1 compared to stimulation by TGF-β1 alone (Chawla and Ghosh, Acta Biomater 2018, 69:131- 45). These discrepancies may be due to IL-6 presence in the CXCL8 + TGF-β cocktail. LOX is known as both a pro-fibrotic role in transcriptional regulation (Iturbide et al., FEBS J 2015, 282:1768-73) and as an enzyme responsible for collagen crosslinking (Chen et al., J Drug Target 2019, 27:790-6) and is therefore involved in multiple steps of the wound healing process. Results show that CXCL8 has a synergistic effect on TGF-β1-induced LOX production (FIG.7). Conversely, a previous study found LOX levels to be significantly upregulated in groups treated with TGF-β1 + IL-6 + CXCL8 or TGF-β1 alone, but no differences were noted between the two groups in this study (Chawla and Ghosh, Acta Biomater 2018, 69:131-45). This poses IL-6 to have a possible agonistic effect on the complementary effect of CXCL8 (also known as interleukin 8; IL-8) on TGF- β1-induced LOX production. Immunofluorescence staining was performed to evaluate the effect of angiogenic chemokines alone and in cocktails on the expression of ECM-related proteins in human dermal fibroblast cells from healthy patients. This included CXCL8, CXCL1 and CCL2 chemokines alone or in combination, with and without prior TGF-β stimulation. This is biologically relevant as both CXCL1 and CXCL88123-112369-02 05552are high in serum levels of scleroderma SSc patients (Lee et al., Arthritis Rheum 2007, 56:2443-8). Compared to untreated cells, cells treated with CXCL8 had higher expression of LOX (FIGS.7A, 7C) and pSMAD2 (FIGS.7B, 7D). Fibronectin (FIGS.6A, 6C) and DCN (FIG.8B, D) protein levels were not significantly altered, although it has been shown previously that CXCL8 decreases DCN expression at the gene level (Cabello-Verrugio et al., J Biol Chem 2012, 287:6773-87; Wu et al., Eur J Med Res 2007, 12:360-8). Comparison of stimulation with the C4 cocktail (CXCL1 + CXCL8) versus CXCL8 alone in TGF-β-activated fibroblasts, there were significantly decreased expression of LOX, fibronectin, and decorin, which may suggest CXCL1 interference in CXCL8-mediation of TGF-β activity in fibroblasts. RNA Sequence analysis of the chemokine cocktail system was used to further investigate the effects of chemokine signaling on primary human fibroblast ECM production and elucidate the gene expression changes induced by the stimulation of chemokines individually or in concert. An enrichment of ECM / collagen related pathways was identified which was associated with ELR+ / TGF- β stimulation (FIG.9). Taking a closer look at the differentially regulated genes within that term, notable genes were differentially regulated between CXCL1 + TGF-β and CXCL8 + TGF-β treatments to include LTBP1, MFAP2, LOXL3, CAPN2, FN1, NID2, FBLN5, FBLN1, COL1A1, FURIN, DCN, and TGFβ1 (FIG.10). The log2 fold change of these genes showed that CXCL8 + TGF-β upregulates FN1, while CXCL1 + TGF-β or C4 + TGF-β downregulates FN1 expression compared to controls (FIG.10). On the other hand, C4 + TGF-β decreases COL1A1 and DCN expression, while individually simulating TGF-β activated fibroblasts with CXCL8 or CXCL1 achieves the opposite (FIG.10), which aligns with previous findings (FIG.6). Taken together, this suggests direct targeting of CXCL8 may mitigate fibroblast ECM protein production. Genes identified in signature studies associated with focal adhesion, migration and junction of ECM components compared to TGF-β-stimulated controls in the CXCL8 vs. TGF-β treatment group, which suggests a broadly conserved cellular response to increased fibrotic ECM production with CXCL8 within fibrotic skin microenvironment. Of the differentially expressed genes (DEGs) identified in CXCL8 + TGF-β vs. control and TGF-β vs. controls, TIMP1, LTBP4, COL1A1, COL1A2, and FN1 signature genes are also featured biomarkers in SSc (Christmann et al., Arthritis Rheumatol 2014, 66:714-25; Kikuchi et al., J Am Acad Dermatol 1995, 33:973-8; Lu et al., Lab Invest 2017, 97:591-601; Moon et al., Ann Rheum Dis 2019, 78:817-25). This therefore suggests that responses to ELR+ chemokine stimulation may be an important factor in the TGF-β driven fibrogenic processes in SSc. Fibroblast chemokine autocrine and paracrine signaling acts as an extracellular cue directing fibroblast ECM production, and that dysregulation of the organized proper ELR+ CXC chemokine signaling may thereby be a driver in fibrotic diseases such as SSc. Studies resulted in some speculation if there is crosstalk whereby resident fibroblasts in turn play a role in shaping the ECM. Investigation by Kill et al. found an increase of CXCL8 and collagen 1 production in dermal8123-112369-02 05552fibroblasts after stimulation with SSc IgG’s (Kill et al., Arthritis Res Ther 2014, 16:R29), suggesting crosstalk between innate immune cells and fibroblast ECM production by way of chemokine modulation may also be relevant in disease pathogenesis. Understanding the intersection between fibroblast-ECM interactions and the influences of the immune microenvironment may inform of the understanding of the pathogenesis of SSc and may lead to new therapeutic targets. While chemokines may regulate fibrosis through their known roles as chemoattractants, there is also evidence that they modulate signaling through the TGF-β pathway. One report has shown that CXCL9 regulates TGF-β-induced epithelial to mesenchymal transition through increased cytoplasmic shuttling of the inhibitory SMAD7 (O'Beirne et al., J Immunol 2015, 195:2788-96). CXCL8 directly increases the expression of TGF-βR1 (Hatthachote and Gillespie, Endocrinology 1999, 140:2533-40) and CXCL4 positively regulates TGF-β expression in the liver (Zaldivar et al., Hepatology 2010, 51:1345-53). However, the ability of these chemokines to impact fibrotic pathogenesis and the mechanisms involved remain elusive. Hence, further directives include identifying the mechanism by which chemokine cocktails interface with TGF-β signaling, whether that be direct or downstream. To investigate the effects of cytokine cocktails in SSc-specific disease context, primary human dermal fibroblasts were isolated from patients with varying disease severities. Fibroblasts derived from individuals with a low and high mRSS reacted elicited increased FN1 expression after stimulation with distinct chemokines. CXCL8 increased FN1 expression in low mRSS fibroblasts. There was little effect on high mRSS, which were instead stimulated to increase FN1 expression with CXCL4 and C1 (CXCL4, CXCL9, CXCL10, CXCL11) treatment (FIGS.11A, 11B). This divergence begs the question whether differences in SSc disease severity may manifest from distinct disease mechanisms. Additionally, the response to chemokines and chemokine cocktails differed from what was observed from TGF-β stimulated fibroblasts. For instance, TGF-β activated fibroblasts displayed reduced DCN expression under all chemokine / chemokine cocktail treatments (FIG.4C, FIG.5C). However, SSc-derived fibroblasts from low mRSS and high mRSS increased DCN expression in response to CXCL8 and C2 (CXCL4, CXCL9, CXCL10, CXCL11, CXCL12), respectively. In conclusion, findings from this study reveal evidence that ELR+ chemokines cocktails regulate the TGF-β-induced pro-fibrotic response of fibroblasts, particularly by way of ECM production and processes involved in ECM organization, structure, and degradation. Specifically, studies evidenced that CXCL8 and CXCL1, CXCL8, and CCL2 synergistic cocktails, regulate production of ECM components in TGF-β-activated fibroblasts. The synergy of these chemokine pathways can mediate disease in vivo. From these studies the ECM activity can be altered and the regulatory role of TGF-β in fibrosis signaling in fibroblasts can be determined and modified.8123-112369-02 05552Table 1. Chemokine combinations. Treatments were executed with and without TGF-β stimulation of fibroblasts. Chemokine Combinations – with and without TGF-β Table 2. Known chemokine receptors Chemokine Receptors Table 3. Sequences of primers used for qRT-PCR. Target SEQ Forward Primer SEQ ID Reverse Primer Gene ID NO: NO: G A C 8123-112369-02 05552Target SEQ Forward Primer SEQ ID Reverse Primer Gene ID NO: NO: Human 19 AAACACTTTCCTGCTCCTCTC 20 CAGAGCTTTGGCTAGGAATGA It will be apparent that the precise details of the methods or compositions described may be varied or modified without departing from the spirit of the described aspects of the disclosure. We claim all such modifications and variations that fall within the scope and spirit of the claims below.

Claims

8123-112369-02 05552CLAIMS 1. A method of treating or inhibiting fibrosis in a subject, comprising administering to the subject an effective amount of a chemokine cocktail comprising: two or more of a CXCL4 protein, a CXCL9 protein, a CXCL10 protein, and a CXCL11 protein, or biologically active fragments or variants thereof; two or more of a CXCL4 protein, a CXCL9 protein, a CXCL10 protein, a CXCL11 protein and a CXCL12 protein, or biologically active fragments or variants thereof; or a CXCL1 protein and a CXCL8 protein, or biologically active fragments or variants thereof.

2. The method of claim 1, wherein the CXCL1, CXCL4, CXCL8, CXCL9, CXCL10, CXCL11, and / or CXCL12 proteins are human proteins.

3. The method of claim 1, wherein the CXCL1, CXCL4, CXCL8, CXCL9, CXCL10, CXCL11, and / or CXCL12 protein comprises at least one chemical modification.

4. The method of claim 1, wherein: the amino acid sequence of the CXCL1 protein is at least 95% identical to SEQ ID NO: 1; the amino acid sequence of the CXCL4 protein is at least 95% identical to SEQ ID NO: 2; the amino acid sequence of the CXCL8 protein is at least 95% identical to SEQ ID NO: 3; the amino acid sequence of the CXCL9 protein is at least 95% identical to SEQ ID NO: 4; the amino acid sequence of the CXCL10 protein is at least 95% identical to SEQ ID NO: 5; the amino acid sequence of the CXCL11 protein is at least 95% identical to SEQ ID NO: 6; and / or the amino acid sequence of the CXCL12 protein is at least 95% identical to SEQ ID NO:

7.

5. The method of claim 1, wherein: the amino acid sequence of the CXCL1 protein comprises or consists of SEQ ID NO: 1; the amino acid sequence of the CXCL4 protein comprises or consists of SEQ ID NO: 2; the amino acid sequence of the CXCL8 protein comprises or consists of SEQ ID NO: 3; the amino acid sequence of the CXCL9 protein comprises or consists of SEQ ID NO: 4; the amino acid sequence of the CXCL10 protein comprises or consists of SEQ ID NO: 5; the amino acid sequence of the CXCL11 protein comprises or consists of SEQ ID NO: 6; and / or the amino acid sequence of the CXCL12 protein comprises or consists of SEQ ID NO: 7.8123-112369-02 055526. The method of claim 1, wherein the chemokine cocktail comprises two or more of: a CXCL4 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence at least 95% identical to SEQ ID NO:

6.

7. The method of claim 6, wherein the chemokine cocktail comprises or consists of: a CXCL4 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence at least 95% identical to SEQ ID NO:

6.

8. The method of claim 1, wherein the chemokine cocktail comprises two or more of: a CXCL4 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence comprising or consisting of SEQ ID NO:

6.

9. The method of claim 8, wherein the chemokine cocktail comprises or consists of: a CXCL4 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 5; and a CXCL11 protein having an amino acid sequence comprising or consisting of SEQ ID NO:

6.

10. The method of claim 1, wherein the chemokine cocktail comprises two or more of: a CXCL4 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 6; and8123-112369-02 05552a CXCL12 protein having an amino acid sequence at least 95% identical to SEQ ID NO:

7.

11. The method of claim 10, wherein the chemokine cocktail comprises or consists of: a CXCL4 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 6; and a CXCL12 protein having an amino acid sequence at least 95% identical to SEQ ID NO:

7.

12. The method of claim 1, wherein the chemokine cocktail comprises two or more of: a CXCL4 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 6; and a CXCL12 protein having an amino acid sequence comprising or consisting of SEQ ID NO:

7.

13. The method of claim 12, wherein the chemokine cocktail comprises or consists of: a CXCL4 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 2; a CXCL9 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 4; a CXCL10 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 5; a CXCL11 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 6; and a CXCL12 protein having an amino acid sequence comprising or consisting of SEQ ID NO:

7.

14. The method of claim 1, wherein the chemokine cocktail comprises: a CXCL1 protein having an amino acid sequence at least 95% identical to SEQ ID NO: 1; and a CXCL8 protein having an amino acid sequence at least 95% identical to SEQ ID NO:

3.

15. The method of claim 14, wherein the chemokine cocktail comprises or consists of:8123-112369-02 05552a CXCL1 protein having an amino acid sequence comprising or consisting of SEQ ID NO: 1; and a CXCL8 protein having an amino acid sequence comprising or consisting of SEQ ID NO:

3.

16. The method of claim 1, wherein the fibrosis is fibrosis of the skin, lung, heart, kidney or liver.

17. The method of claim 1, wherein the subject is human.

18. A method for increasing extracellular matrix (ECM) production and / or treating a wound in a subject, comprising administering to the subject an effective amount of a chemokine cocktail comprising: a CXCL1 protein and a CXCL8 protein, or biologically active fragments or variants thereof; or a CXCL1 protein, a CXCL8 protein, and a CCL2 protein, or biologically active fragments or variants thereof.

19. The method of claim 18, wherein the CXCL1, CXCL8 and / or CCL2 proteins are human proteins.

20. The method of claim 18, wherein the CXCL1, CXCL8 and / or CCL2 protein comprises at least one chemical modification.

21. The method of claim 18, wherein: the amino acid sequence of the CXCL1 protein is at least 95% identical to SEQ ID NO: 1; the amino acid sequence of the CXCL8 protein is at least 95% identical to SEQ ID NO: 3; and / or the amino acid sequence of the CCL2 protein is at least 95% identical to SEQ ID NO:

8.

22. The method of claim 18, wherein: the amino acid sequence of the CXCL1 protein comprises or consists of SEQ ID NO: 1; the amino acid sequence of the CXCL8 protein comprises or consists of SEQ ID NO: 3; and / or the amino acid sequence of the CCL2 protein comprises or consists of SEQ ID NO:

8.

23. The method of claim 18, wherein the subject is human.8123-112369-02 0555224. The method of claim 18, wherein the chemokine cocktail is formulated for topical, intranasal, inhalation, intravenous, intramuscular, intradermal, or subcutaneous administration.

25. The method of claim 1, wherein the chemokine cocktail is formulated for topical, intranasal, inhalation, intravenous, intramuscular, intradermal, or subcutaneous administration.

Images