Peptides having anti-inflammatory activity and compositions containing the same

Abstract

To provide peptides with anti-inflammatory activity, and compositions comprising the same.SOLUTION: The present invention relates to a peptide having any one amino acid sequence of SEQ ID NO: 1 to SEQ ID NO: 161, a peptide being a fragment of the sequences, and a peptide having 80% or more sequence homology with the peptide sequences, and an anti-inflammatory composition comprising such a peptide as an active ingredient.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to peptides having anti-inflammatory activity and compositions containing the same. [Background technology]

[0002] Inflammation is one of the body's defense reactions to prevent damage to living tissues caused by external physical stimuli, chemical stimuli such as contact with various allergy-inducing substances, or the invasion of microorganisms such as bacteria, fungi, or viruses.

[0003] Inflammatory signals are produced via the cyclooxygenase (COX) pathway or lipoxygenase (LOX) pathway, producing prostaglandins, thromboxanes, etc. When inflammatory signals are transmitted, various changes occur in the body, including the dilation of blood vessels in the necessary areas, increasing blood supply and concentrating blood cells, such as neutrophils, that are necessary for the inflammatory response. However, if such a defense response of the body occurs abnormally or excessively, various inflammatory diseases can develop. To prevent this, drugs have been developed that can suppress excessive inflammatory responses by blocking the inflammatory signaling pathway by inhibiting enzymes in the inflammatory signaling pathway (e.g., COX-1, COX-2, 5-LOX, 12-LOX, etc.).

[0004] Depending on the duration of the reaction, inflammation can be divided into acute inflammation (an immediate, non-specific reaction lasting several days to several weeks), chronic inflammation (a delayed, specific reaction lasting several weeks or more), and subacute inflammation (an intermediate stage between acute and chronic inflammation, characterized by a mixed product of polynuclear cells and mononuclear cells).

[0005] In addition to peptide factors, factors that induce inflammation include lipid factors such as prostaglandins, leukotrienes, and platelet-activating factors, inflammatory factor-synthesizing enzymes, free radicals such as nitric oxide (NO), various types of cell adhesion molecules, the immune system, and coagulation factors.

[0006] The currently known mechanism of inflammation is that cell damage caused by external biological factors (bacteria, viruses, parasites), physical factors (mechanical stimuli, heat, radiation, electricity), or chemical factors results in the release of histamine and kinins, which in turn causes vasodilation, increased capillary permeability, and the accumulation of macrophages at the site of inflammation, resulting in increased blood flow to the infected area, edema, migration of immune cells and antibodies, pain, fever, and other symptoms.

[0007] Currently available anti-inflammatory drugs include synthetic drugs such as ibuprofen, antihistamines, steroids, cotison, immunosuppressants, and immunostimulants. However, these drugs often only provide temporary therapeutic effects, merely relieve symptoms, or have numerous side effects, such as hypersensitivity reactions and immune system deterioration, making it difficult to fundamentally treat inflammation. Therefore, research has recently been conducted into substances that can inhibit the expression of inflammation-related proteins in order to effectively alleviate inflammation. However, the anti-inflammatory substances developed through such research have been plagued by several side effects. Anti-inflammatory drugs with various mechanisms, including nonsteroidal anti-inflammatory drugs (NSAIDs) and steroidal anti-inflammatory drugs (SAIDs), have been developed. However, they not only exhibit significant side effects but also do not fundamentally suppress the inflammatory response. Therefore, there remains a need for more effective, safe, and cost-effective drugs. For example, nonsteroidal anti-inflammatory drugs (NSAIDs), which are used to treat chronic inflammatory diseases such as acute arthritis or rheumatoid arthritis, are known to inhibit not only COX-2 enzyme but also COX-1 enzyme, resulting in side effects such as gastrointestinal disorders. [Prior art documents] [Patent documents]

[0008] [Patent Document 1] KR2012-013996A [Patent Document 2] KR2012-0133661A [Patent Document 3] KR2011-0060940A [Patent Document 4] US2011-0150873A1 [Non-patent literature]

[0009] [Non-Patent Document 1] Bonaldi T et al., EMBOJ, (22)5551-60, 2003 [Non-patent document 2] Yankner BA et al., Science (New York, NY) [1990, 250(4978): 279-282] [Non-patent document 3] Dahlgren KN et al., J. Biol. Chem. 277: 32046-32053, 2002 Summary of the Invention [Problem to be solved by the invention]

[0010] The present inventors discovered that peptides derived from telomerase have anti-inflammatory activity, and have completed the present invention.

[0011] Therefore, an object of the present invention is to provide a novel peptide.

[0012] Another object of the present invention is to provide a polynucleotide encoding the novel peptide.

[0013] Another object of the present invention is to provide a peptide having anti-inflammatory activity.

[0014] It is still another object of the present invention to provide an anti-inflammatory composition which uses a peptide having anti-inflammatory activity as an active ingredient.

[0015] It is yet another object of the present invention to provide a cosmetic composition using a peptide having anti-inflammatory activity as an active ingredient.

[0016] It is still another object of the present invention to provide a pharmaceutical composition using a peptide having anti-inflammatory activity as an active ingredient. [Means for solving the problem]

[0017] According to one aspect of the present invention, there is provided a peptide having anti-inflammatory activity, the peptide comprising any one or more amino acid sequences of SEQ ID NOs: 1 to 161, a peptide having at least 80% sequence identity with the amino acid sequence, or a fragment of the peptide.

[0018] According to another aspect of the invention, the fragment may be a fragment of 3 or more amino acids, for example, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 amino acids.

[0019] According to another aspect of the invention, the peptide consists of 30 or fewer amino acids. For example, the fragment may be a fragment of 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, or 8 amino acids.

[0020] According to another aspect of the present invention, the peptide consists of any one of the amino acid sequences of SEQ ID NOs: 1 to 161.

[0021] According to another aspect of the present invention, the peptide may comprise any one amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 6, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NOs: 14 to 21, SEQ ID NOs: 23 to 37, SEQ ID NOs: 39 to 44, SEQ ID NOs: 47 to 53, SEQ ID NOs: 55 to 61, SEQ ID NOs: 63 to 82, SEQ ID NOs: 84 to 94, SEQ ID NO: 96, SEQ ID NOs: 99 to 104, SEQ ID NOs: 107 to 109, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NOs: 120 to 122, SEQ ID NO: 124, SEQ ID NOs: 129 to 133, SEQ ID NOs: 142 to 144, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 149 and SEQ ID NOs: 155 to 159.

[0022] According to another aspect of the present invention, the peptide may comprise any one amino acid sequence selected from the group consisting of SEQ ID NOs: 15 to 18, SEQ ID NOs: 23 to 27, SEQ ID NO: 29, SEQ ID NOs: 31 to 34, SEQ ID NOs: 39 to 41, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NOs: 51 to 53, SEQ ID NOs: 55 to 58, SEQ ID NO: 61, SEQ ID NOs: 65 to 68, SEQ ID NO: 70, SEQ ID NOs: 73 to 79, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NOs: 84 to 87, SEQ ID NOs: 89 to 94, SEQ ID NO: 96, SEQ ID NO: 99, SEQ ID NOs: 101 to 104, SEQ ID NOs: 107 to 109, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NOs: 129 to 132, SEQ ID NOs: 142 to 144, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 149, and SEQ ID NOs: 157 to 159.

[0023] According to another aspect of the present invention, the peptide may comprise any one amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 5, SEQ ID NO: 7, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 15, SEQ ID NOs: 17 to 27, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NOs: 32 to 53, SEQ ID NOs: 55 to 60, SEQ ID NO: 67, SEQ ID NO: 68, SEQ ID NO: 70, SEQ ID NOs: 72 to 82, SEQ ID NOs: 84 to 92, SEQ ID NO: 94, SEQ ID NOs: 99 to 112, SEQ ID NO: 114, SEQ ID NOs: 127 to 144, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 149, SEQ ID NO: 151 and SEQ ID NOs: 153 to 161.

[0024] According to another aspect of the present invention, the peptide may comprise any one amino acid sequence selected from the group consisting of SEQ ID NO:1 to SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17 to SEQ ID NO:23, SEQ ID NO:25 to SEQ ID NO:27, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:33 to SEQ ID NO:43, SEQ ID NO:156, SEQ ID NO:157, and SEQ ID NO:159.

[0025] According to another aspect of the invention, the peptide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:52, SEQ ID NO:57, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO: 2, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:91, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:135, SEQ ID NO:146, SEQ ID NO:151, SEQ ID NO:154 and SEQ ID NO:156.

[0026] According to another aspect of the invention, the peptide is also derived from human telomerase.

[0027] According to one aspect of the present invention, there is provided a polynucleotide encoding a peptide having anti-inflammatory activity, the peptide comprising any one of the amino acid sequences of SEQ ID NOs: 1 to 161, or a peptide having at least 80% sequence identity with said amino acid sequence, or a peptide which is a fragment of said peptide.

[0028] In another aspect of the invention, the peptide is also a polynucleotide encoding 30 or fewer amino acids, for example, a fragment consisting of 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9 or 8 amino acids.

[0029] According to another aspect of the present invention, the peptide is also a polynucleotide encoding a peptide consisting of any one of the amino acid sequences of SEQ ID NOs: 1 to 161.

[0030] According to another aspect of the present invention, the peptide is a polynucleotide encoding a peptide derived from human telomerase.

[0031] According to one aspect of the present invention, there is provided an anti-inflammatory composition comprising, as an active ingredient, a peptide comprising any one of the amino acid sequences of SEQ ID NOs: 1 to 161, a peptide having 80% or more sequence identity with the amino acid sequence, or a peptide that is a fragment thereof.

[0032] In another aspect of the present invention, the composition comprises a peptide consisting of 30 amino acids or less (see above).

[0033] In the composition according to another aspect of the present invention, the peptide may consist of any one of the amino acid sequences of SEQ ID NOs: 1 to 161.

[0034] In another aspect of the present invention, the composition is one in which the peptide is derived from human telomerase.

[0035] The compositions according to other aspects of the present invention are also for use in treating or preventing inflammatory diseases.

[0036] The composition according to another aspect of the present invention is also a cosmetic composition for improving or preventing skin inflammation.

[0037] The composition according to another aspect of the present invention is also a pharmaceutical composition for treating or preventing an inflammatory disease.

[0038] The composition according to another aspect of the present invention is also a food composition for improving or preventing inflammation.

[0039] In another aspect of the present invention, the inflammatory disease is (1) a systemic or local inflammatory disease (e.g., allergy; immune complex disease; hay fever; hypersensitivity shock; toxin-resistant shock; cachexia, hyperthermia; granulomatosis; or sarcoidosis); (2) a gastrointestinal disease (e.g., appendicitis; gastric ulcer; duodenal ulcer; peritonitis; pancreatic enteritis; ulcerative, acute, or ischemic colitis; cholangitis); cholecystitis, steatorrhea, hepatitis, Crohn's disease, or Whipple's disease; (3) skin-related diseases (e.g., psoriasis, burns, sunburn, dermatitis, urticarial warts or wheals); (4) cardiovascular diseases (e.g., vasculitis, vasculitis, endocarditis, arteritis, atherosclerosis, thrombophlebitis, pericarditis, congestive heart failure, myocarditis, myocardial ischemia, periarteritis nodosa, recurrent stenosis, Burger's disease, or Lewy's disease) (5) respiratory diseases (e.g., asthma; epiglottitis; bronchitis; emphysema; rhinitis; cystic fibrosis; epileptic pneumonia; chronic obstructive pulmonary disease (COPD); adult respiratory syndrome; pneumoconiosis; alveolitis; bronchiolitis; pharyngitis; pleurisy; or sinusitis); (6) bone, joint, muscle, and connective tissue-related diseases (e.g., granulomatous granulomatosis; arthritis; arthralgia; osteomyelitis; dermatomyositis) (7) diseases of the genitourinary system (e.g., epididymitis, vaginitis, prostatitis, or urethritis); (8) diseases of the central or peripheral nervous system (e.g., Alzheimer's disease, meningitis, encephalitis, multiple sclerosis, cerebral infarction, cerebral embolism, Guillain-Barre syndrome, etc.) syndrome); neuritis; neuralgia; bone marrow trauma; paralysis; or uveitis; (9) viral (e.g., influenza; respiratory cytoplasmic virus; HIV; hepatitis B virus; hepatitis C virus; or herpes virus) infectious diseases (e.g., dengue fever; or septicemia), fungal infectious diseases (e.g., candidiasis), or other microbial infectious diseases such as bacterial or parasitic diseases (e.g., disseminated bacteremia; malaria; filariasis; or amebiasis); (10) other autoimmune diseases (e.g., thyroiditis; lupus; Goodpasture's syndrome; allograft rejection; graft-versus-host disease; or diabetes); and (11) cancer or neoplastic diseases (e.g., Hodgkin's disease).

[0040] According to one aspect of the present invention, there is provided a method for preventing or treating an inflammatory disease, which comprises administering the above-mentioned anti-inflammatory composition.

[0041] According to one aspect of the present invention, there is provided a kit for preventing or treating an inflammatory disease, comprising a peptide comprising one or more amino acid sequences selected from SEQ ID NOs: 1 to 161, a peptide having 80% or more sequence identity with the amino acid sequence, or a peptide which is a fragment thereof, or a composition comprising the same, and instructions disclosing one or more of the dosage, administration route, administration frequency, and indications for the peptide or composition comprising the same. [Effects of the Invention]

[0042] The peptides according to the present invention, which have any one of SEQ ID NOS: 1 to 161, or which have a sequence with 80% homology to the above sequences, or peptide fragments thereof, have excellent anti-inflammatory effects. Therefore, compositions containing the peptides of the present invention can be used as pharmaceutical or cosmetic compositions for their anti-inflammatory effects and are widely used in the treatment and prevention of various inflammatory diseases. [Brief explanation of the drawings]

[0043] [Figure 1] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 2] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 3] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 4] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 5] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 6]These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 7] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 8] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 9] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 10] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 11] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 12] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 13] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 14] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 15] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 16] These are the results of screening for the TNF-α inhibitory effect on monocytes. [Figure 17] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 18] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 19] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 20] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 21] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 22] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 23] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 24] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 25] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 26] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 27] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 28] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 29] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 30] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 31] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 32] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 33] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 34] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 35] These are the results of screening for the TNF-α inhibitory effect on the cell line THP-1. [Figure 36]Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 37] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 38] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 39] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 40] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 41] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 42] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 43] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 44] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 45] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 46] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 47] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 48] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 49] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 50] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 51] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 52] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 53] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 54] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 55] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 56] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 57] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 58] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 59] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 60] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 61] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 62] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 63] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 64] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 65]Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 66] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 67] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 68] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 69] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 70] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 71] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 72] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 73] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 74] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 75] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 76] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 77] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 78] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 79] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 80] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 81] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 82] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 83] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 84] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 85] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 86] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 87] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 88] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 89] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 90] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 91] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 92] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 93] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 94] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 95] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 96] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 97] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 98] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 99] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 100] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 101] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 102] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 103] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 104] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 105] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 106] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 107] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. [Figure 108] Western blot analysis of selected peptides showing intracellular HMGB1 accumulation. DETAILED DESCRIPTION OF THE INVENTION

[0044] The present invention can be modified in various ways and has various embodiments, and will be described in more detail below. However, it should be understood that the present invention is not limited to a specific embodiment, but includes all modifications, equivalents, and alternatives within the spirit and technical scope of the present invention. In describing the present invention, if a detailed description of related publicly known technology is deemed to obscure the gist of the present invention, the detailed description will be omitted.

[0045] Telomeres are genetic material found repeatedly at the ends of chromosomes and are known to prevent damage to the chromosome or its subsequent attachment to other chromosomes. Each time a cell divides, the length of the telomere gradually shortens. However, after a certain number of cell divisions, the telomere becomes so short that the cell stops dividing and dies. It is known that lengthening telomeres can extend the lifespan of cells. For example, cancer cells secrete an enzyme called telomerase to prevent telomere shortening, allowing them to survive and continue to grow. The present inventors discovered that numerous peptides derived from telomerase have anti-inflammatory activity, leading to the completion of the present invention.

[0046] One aspect of the present invention provides a peptide having anti-inflammatory activity, which comprises any one or more amino acid sequences of SEQ ID NOs: 1 to 161, a peptide having 80% or more sequence identity with the amino acid sequence, or a fragment thereof.

[0047] The peptides set forth in SEQ ID NOs: 1 to 161 are as shown in Table 1 below. SEQ ID NO: 162 is the sequence of the full-length human telomerase protein. SEQ ID NO: 163 shows a peptide composed of 16 amino acids derived from telomerase.

[0048] The "names" in Table 1 below are used to distinguish the peptides. In another aspect of the present invention, one or more of the peptides set forth in SEQ ID NOs: 1 to 161 include "synthetic peptides" synthesized by selecting peptides at the corresponding positions from peptides contained in telomerase. As used herein, "pep" is a general term referring to a peptide having any one of the sequences set forth in SEQ ID NOs: 1 to 161, or a peptide having 80% or more sequence identity to such a sequence, or a fragment of such a sequence.

[0049] [Table 1]

[0050] [Table 2]

[0051] [Table 3]

[0052] [Table 4]

[0053] [Table 5]

[0054] [Table 6]

[0055] One aspect of the present invention provides a polynucleotide encoding a peptide having anti-inflammatory activity, the peptide comprising one or more amino acid sequences selected from SEQ ID NOS: 1 to 161, a peptide having 80% or more sequence identity with the amino acid sequence, or a fragment thereof. The polynucleotide can be used to mass-produce the peptide. For example, the peptide can be mass-produced by introducing a vector containing a polynucleotide encoding the peptide into a host cell and culturing the cell.

[0056] The peptides disclosed herein include peptides with 80% or more, 85% or more, 90% or more, 95% or more, 96% or more, 97% or more, 98% or more, or 99% or more sequence identity. The peptides disclosed herein may also include peptides comprising SEQ ID NO: 1 or fragments thereof, and peptides that vary by one or more amino acids, two or more amino acids, three or more amino acids, four or more amino acids, five or more amino acids, six or more amino acids, or seven or more amino acids.

[0057] As used herein, "homology" and "sequence identity" are used interchangeably and refer to the degree of sequence overlap between two amino acids (or, as related, nucleic acids). Although the term "sequence identity" is not specifically used herein with respect to peptides or nucleic acids, sequence identity is understood to be a function of the sequence identity (n ref -n dif )*100 / n ref The formula is used to calculate the maximum number of matches when aligning two sequences. dif is the total number of non-matching residues between the two sequences, ref means the total number of residues of the shorter sequence in the two sequences. For example, the sequence identity of the DNA sequence agtcagtc with the sequence aatcaatc is 75% when calculated using the above formula (n ref =8, n dif =2).

[0058] In one aspect of the present specification, sequence identity was determined by the following conventional method: Smith and Waterman, 1981, Adv. Appl. Math. 2:482, by the search for similarity method of Pearson & Lipman, 1988, Proc. Natl. Acad. Sci. USA 85:2444, using the CLUSTAL W algorithm of Thompson et al., 1994, Nucleic Acids Res 22:467380, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group). The BLAST algorithm (Altschul et al., 1990, Mol. Biol. 215:403-10), for which software may be obtained through the National Center for Biotechnology Information (www.ncbi.nlm.nih.gov / ), may also be used. using any of the mentioned algorithms, the default parameters for "Window" length, gap penalty, etc.

[0059] In one aspect of the present invention, amino acid changes are made to alter the physicochemical properties of the peptide, for example, to improve the thermal stability of the peptide, alter its substrate specificity, or change its pH optimum.

[0060] In one aspect of the present invention, a peptide comprising any one or more amino acid sequences of SEQ ID NOs: 1 to 161, a peptide having 80% or more sequence identity with the amino acid sequence, or a peptide which is a fragment thereof may be composed of 30 or less amino acids.

[0061] In one aspect of the present invention, peptides having the sequences of SEQ ID NOs: 1 to 161, peptides that are fragments of the sequences of SEQ ID NOs: 1 to 161, or peptides that have 80% or more sequence identity to the peptide sequences include peptides derived from telomerase, specifically human (Homo sapiens) telomerase.

[0062] As used herein, the term "amino acid" refers not only to the 22 standard amino acids naturally incorporated into peptides, but also to D-isomers and modified amino acids. Accordingly, in one aspect of the present invention, a peptide may also contain a D-amino acid. Meanwhile, in another aspect of the present invention, a peptide may contain non-standard amino acids that have undergone post-translational modification. Examples of post-translational modifications include phosphorylation, glycosylation, acylation (e.g., acetylation, myristoylation, and palmitoylation), alkylation, carboxylation, hydroxylation, glycation, biotinylation, ubiquitinylation, chemical changes (e.g., beta-elimination thalimidation, deamidation), and structural changes (e.g., disulfide bridge formation). It also includes amino acid changes, such as changes at the amino group, carboxylic acid group, or side chain, that occur due to chemical reactions that occur during the conjugation process with a cross linker to form a peptide conjugate.

[0063] The peptides disclosed herein may be wild-type peptides identified and isolated from natural sources. Alternatively, the peptides disclosed herein may be artificial variants, which contain an amino acid sequence in which one or more amino acids have been substituted, deleted, and / or inserted compared to a peptide that is a fragment of SEQ ID NO: 1. Amino acid changes in wild-type polypeptides, as well as in artificial variants, include conservative amino acid substitutions that do not significantly affect protein folding and / or activity. Examples of conservative substitutions are within the following groups: basic amino acids (arginine, lysine, and histidine), acidic amino acids (glutamic acid and aspartic acid), polar amino acids (glutamine and asparagine), hydrophobic amino acids (leucine, isoleucine, valine, and methionine), aromatic amino acids (phenylalanine, tryptophan, and tyrosine), and small amino acids (glycine, alanine, serine, and threonine). Generally, amino acid substitutions that do not alter specific activity are known in the art. The most commonly occurring exchanges are Ala / Ser, Val / Ile, Asp / Glu, Thr / Ser, Ala / Gly, Ala / Thr, Ser / Asn, Ala / Val, Ser / Gly, Tyr / Phe, Ala / Pro, Lys / Arg, Asp / Asn, Leu / Ile, Leu / Val, Ala / Glu, and Asp / Gly, and their opposites. Other examples of conservative substitutions are set out in Table 2 below.

[0064] [Table 7]

[0065] Substantial variations in the biological properties of peptides are achieved by selecting substitutions that differ significantly in (a) their effect on maintaining the structure of the polypeptide backbone in the region of substitution, e.g., sheet or helical conformation, (b) their effect on maintaining the charge or hydrophobicity of the molecule at the target site, or (c) their effect on maintaining the bulk of the side chain. Natural residues are divided into the following groups based on common side chain properties:

[0066] (1) Hydrophobic: norleucine, met, ala, val, leu, ile; (2) Neutral hydrophilic: cys, ser, thr; (3) Acidic: asp, glu; (4) basic: asn, gln, his, lys, arg; (5) residues that influence chain orientation: gly, pro; and (6) Aromatics: trp, tyr, phe.

[0067] Non-conservative substitutions are made by exchanging a member of one of these classes for another. Any cysteine ​​residue not involved in maintaining the proper conformation of the peptide is generally substituted with serine to improve the oxidative stability of the molecule and prevent aberrant cross-linking. Conversely, cysteine ​​bonds can be added to the peptide to improve its stability.

[0068] Another type of amino acid variant of a peptide is one that alters the glycosylation pattern of the antibody, by which is meant the deletion of one or more carbohydrate residues found in the peptide and / or the addition of one or more glycosylation sites that are not present in the peptide.

[0069] Glycosylation of peptides is typically either N-linked or O-linked. N-linked refers to the attachment of the carbohydrate residue to the side chain of an asparagine residue. The tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate residue to the asparagine side chain. Thus, the presence of one of these tripeptide sequences in a polypeptide creates a potential glycosylation site. O-linked glycosylation refers to the attachment of one of the sugars N-acetylgalactosamine, galactose, or xylose to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine can also be used.

[0070] Glycosylation sites are conveniently added to the peptide by altering the amino acid sequence such that it contains one or more of the above-described tripeptide sequences (for N-linked glycosylation sites). Such alterations may also be made by adding, or substituting, one or more serine or threonine residues to the sequence of the original antibody (for O-linked glycosylation sites).

[0071] In one aspect of the present invention, a polynucleotide is a nucleic acid molecule, which may be a naturally occurring or artificial DNA or RNA molecule, and may be single-stranded or double-stranded. The nucleic acid molecule may be one or more nucleic acid molecules of the same type (e.g., having the same nucleoside sequence) or of another type, including, but not limited to, DNA, cDNA, decoy DNA, RNA, siRNA, miRNA, shRNA, stRNA, snoRNA, snRNA, PNA, antisense oligomers, plasmids, and other modified nucleic acids.

[0072] HMGB1 protein is known to function as an inflammatory cytokine by being acetylated in the nucleus in response to external stimuli, translocating to the cytoplasm, and then secreting it to the extracellular space. Because HMGB1 protein is secreted to the extracellular space when inflammation is present, the serum of patients with inflammatory diseases such as Churg-Strauss syndrome, rheumatoid arthritis, and Sjögren's syndrome contains significantly higher amounts of HMGB1 protein than normal individuals. Therefore, regardless of the type of inflammation-inducing stimulus, if the amount of HMGB1 protein in the cell nucleus is high, it means that HMGB1 protein is not secreted to the extracellular space, and therefore inflammation is suppressed.

[0073] In one aspect of the present invention, treatment of cells with peptides having the sequences of SEQ ID NOs: 1 to 161, peptides that are fragments of the sequences of SEQ ID NOs: 1 to 161, or peptides that share 80% or more sequence identity with the peptide sequences increases the amount of HMGB1 protein in the cell nucleus, indicating that peptides having the sequences of SEQ ID NOs: 1 to 161, peptides that are fragments of the sequences of SEQ ID NOs: 1 to 161, or peptides that share 80% or more sequence identity with the peptide sequences have excellent anti-inflammatory effects.

[0074] Furthermore, peptides having the sequences of SEQ ID NOs: 1 to 161 according to one aspect of the present invention, peptides that are fragments of the sequences of SEQ ID NOs: 1 to 161, or peptides that have 80% or more sequence homology to the peptide sequences have the advantages of low intracellular toxicity and high in vivo stability.

[0075] As used herein, the term "inflammatory disease" is a broad concept that includes any disease associated with inflammation, such as a disease whose main cause is inflammation or a disease that causes inflammation.Specifically, the inflammatory diseases include (1) systemic or local inflammatory diseases (e.g., allergies; immune complex diseases; hay fever; hypersensitivity shock; toxin-resistant shock; cachexia, hyperpyrexia; granulomatosis; or sarcoidosis); (2) gastrointestinal diseases (e.g., appendicitis; gastric ulcer; duodenal ulcer; peritonitis; pancreatic enteritis; ulcerative, acute, or ischemic colitis; cholangitis; cholecystitis; steatorrhea). (3) skin-related diseases (e.g., psoriasis; burns; sunburn; dermatitis; urticarial warts or wheals); (4) cardiovascular diseases (e.g., vasculitis; vasculitis; endocarditis; arteritis; atherosclerosis; thrombophlebitis; pericarditis; congestive heart failure; myocarditis; myocardial ischemia; periarteritis nodosa; recurrent stenosis; Burger's disease; or rheumatic fever). (5) respiratory diseases (e.g., asthma, epiglottitis, bronchitis, emphysema, rhinitis, cystic fibrosis, epileptic pneumonia, chronic obstructive pulmonary disease (COPD), adult respiratory syndrome, pneumoconiosis, alveolitis, bronchiolitis, pharyngitis, pleurisy, or sinusitis); (6) bone, joint, muscle, and connective tissue-related diseases (e.g., eosinophilic granuloma, arthritis, arthralgia, osteomyelitis, dermatomyositis, fasciitis, (7) Genitourinary system diseases (e.g., epididymitis, vaginitis, prostatitis, or urethritis); (8) Central or peripheral nervous system-related diseases (e.g., Alzheimer's disease, meningitis, encephalitis, multiple sclerosis, cerebral infarction, cerebral embolism, Guillain-Barre syndrome, etc.) syndrome); neuritis; neuralgia; bone marrow trauma; paralysis; or uveitis; (9) viral (e.g., influenza; respiratory cytoplasmic virus; HIV; hepatitis B virus; hepatitis C virus; or herpes virus), infectious disease (e.g., dengue fever; or septicemia), fungal infectious disease (e.g., candidiasis); or bacterial, parasitic, and similar microbial infectious disease (e.g., disseminated bacteremia; malaria; filariasis; or amebiasis); (10) autoimmune disease (e.g., thyroiditis; lupus; Goodpasture's syndrome; allograft rejection; graft-versus-host disease; or diabetes); or (11) cancer or neoplastic disease (e.g., Hodgkin's disease).

[0076] Treating the inflammatory component of such diseases has been a primary goal of the global pharmaceutical industry for decades, and numerous useful treatments have been developed. These include corticosteroids (a diverse range of natural, semi-synthetic, and synthetic preparations designed to mimic the effects of cortisol, including prednisolone, methylprednisolone, dexamethasone, betamethasone, fluticasone, etc.), cyclooxygenase inhibitors (non-selective or COX-1 selective, such as indomethacin, sulfasalazine, and aspirin, and more recently COX-2 selective, such as celecoxib), leukotriene blockers (such as montelukast), and small molecule TNF-α synthesis inhibitors (such as thalidomide), as well as infliximab (Remicade). TM ) and adalimumab (Humira Tm Improved monoclonal neutralizing antibodies, including etanercept (Enbrel TM ) anti-TNF, such as TNF receptor fusion proteins.

[0077] In one aspect of the present invention, there is provided an anti-inflammatory composition comprising, as an active ingredient, a peptide comprising any one or more amino acid sequences selected from SEQ ID NOs: 1 to 161, a peptide having 80% or more sequence identity with the amino acid sequence, or a peptide that is a fragment thereof.

[0078] In one aspect, the anti-inflammatory composition according to one aspect of the present invention may contain a peptide comprising one or more amino acid sequences selected from SEQ ID NOS: 1 to 161, a peptide having 80% or more sequence identity to the amino acid sequence, or a peptide fragment thereof, in an amount of 0.1 μg / mg to 1 mg / mg, specifically 1 μg / mg to 0.5 mg / mg, and more specifically 10 μg / mg to 0.1 mg / mg. This range is appropriate not only for achieving the intended effects of the present invention, but also for ensuring both the stability and safety of the composition, and from the perspective of cost-effectiveness.

[0079] The compositions according to one aspect of the present invention may be applied to all animals including humans, dogs, chickens, pigs, cows, sheep, guinea pigs or monkeys.

[0080] In one aspect of the present invention, there is provided a pharmaceutical composition for treating or preventing an inflammatory disease, comprising as an active ingredient a peptide having a sequence selected from the group consisting of SEQ ID NOs: 1 to 161, a peptide which is a fragment of the sequence of SEQ ID NO: 1, or a peptide having 80% or more sequence identity to the peptide sequence. The pharmaceutical composition according to one aspect of the present invention may be administered orally, rectally, transdermally, intravenously, intramuscularly, intraperitoneally, intramedullarily, intradurally, subcutaneously, or the like.

[0081] Dosage forms for oral administration include, but are not limited to, tablets, pills, soft or hard capsules, granules, powders, liquids, or emulsions.Dosage forms for parenteral administration include, but are not limited to, injections, drops, lotions, ointments, gels, creams, suspensions, emulsions, suppositories, patches, or sprays.

[0082] The pharmaceutical composition according to one aspect of the present invention may contain, if necessary, additives such as diluents, excipients, lubricants, binders, disintegrants, buffers, dispersants, surfactants, colorants, flavors, or sweeteners. The pharmaceutical composition according to one aspect of the present invention may be manufactured by a method commonly used in the art.

[0083] The active ingredient of the pharmaceutical composition according to one aspect of the present invention varies depending on the age, sex, and weight of the recipient, the pathological condition and its severity, the route of administration, and the discretion of the prescriber. Determining the dosage based on such factors is within the skill of one of ordinary skill in the art. The daily dosage may be, for example, but is not limited to, 0.1 μg / kg / day to 1 g / kg / day, specifically 1 μg / kg / day to 10 mg / kg / day, more specifically 10 μg / kg / day to 1 mg / kg / day, and even more specifically 50 μg / kg / day to 100 μg / kg / day. The pharmaceutical composition according to one aspect of the present invention is administered once to three times daily, but is not limited thereto.

[0084] In one aspect, the present invention provides an external skin preparation composition for improving or preventing skin inflammation, which contains as an active ingredient a peptide comprising any one or more amino acid sequences selected from SEQ ID NOs: 1 to 161, a peptide having 80% or more sequence identity with the amino acid sequence, or a peptide that is a fragment thereof.

[0085] In another aspect of the present invention, there is provided a cosmetic composition for improving or preventing skin inflammation, which comprises as an active ingredient a peptide comprising any one or more amino acid sequences selected from SEQ ID NOs: 1 to 161, a peptide having 80% or more sequence identity with the amino acid sequence, or a peptide that is a fragment thereof.

[0086] The skin external preparation composition or cosmetic composition according to one aspect of the present invention may be provided in any dosage form suitable for topical application. For example, it may be provided in the form of a solution, an emulsion obtained by dispersing an oily phase in an aqueous phase, an emulsion obtained by dispersing an aqueous phase in an oily phase, a suspension, a solid, a gel, a powder, a paste, a foam, or an aerosol. Such dosage forms may be prepared by methods commonly known in the art.

[0087] The cosmetic composition according to one aspect of the present invention may contain other ingredients that can provide a synergistic effect to the main effect, as long as the ingredients do not impair the main effect. The cosmetic composition according to one aspect of the present invention may further contain a moisturizer, an emollient, a surfactant, an ultraviolet absorber, a preservative, a bactericide, an antioxidant, a pH adjuster, an organic or inorganic pigment, a fragrance, a cooling agent, or an antiperspirant. The amounts of the ingredients can be easily selected by those skilled in the art within a range that does not impair the purpose and effects of the present invention, and the amount may be 0.01 to 5 wt %, specifically 0.01 to 3 wt %, based on the total weight of the cosmetic composition.

[0088] In one aspect of the present invention, the composition provides a food composition for preventing or suppressing inflammation, which comprises as an active ingredient a peptide having a sequence selected from the group consisting of SEQ ID NOs: 1 to 161, a peptide that is a fragment of a sequence of SEQ ID NOs: 1 to 161, or a peptide that has 80% or more sequence identity to the peptide sequence. The dosage form of the food composition according to one aspect of the present invention is not particularly limited, and may be, for example, a tablet, granule, powder, liquid, solid preparation, etc. In addition to the active ingredient, each dosage form may be formulated by a person skilled in the art by appropriately selecting and incorporating ingredients commonly used in the art according to the dosage form or intended use, and when used simultaneously with other ingredients, a synergistic effect occurs.

[0089] Determining the dosage of the active ingredient is within the level of a person skilled in the art, and the daily dosage may be, for example, specifically 1 μg / kg / day to 10 mg / kg / day, more specifically 10 μg / kg / day to 1 mg / kg / day, and even more specifically 50 μg / kg / day to 100 μg / kg / day, but is not limited thereto, and may vary depending on various factors such as the age, health condition, and complications of the subject to be administered.

[0090] In one aspect, the present invention provides a peptide comprising any one or more amino acid sequences selected from SEQ ID NOs: 1 to 161, a peptide having 80% or more sequence identity with the amino acid sequence, or a peptide which is a fragment thereof, for use in the prevention or treatment of inflammatory diseases.

[0091] According to one aspect of the present invention, there is provided a method for preventing or treating an inflammatory disease by providing a peptide to said patient.

[0092] In one aspect of the present invention, there is provided a kit for preventing or treating an inflammatory disease, comprising: a peptide comprising any one or more amino acid sequences selected from SEQ ID NOs: 1 to 161, a peptide having 80% or more sequence identity with the amino acid sequence, or a peptide that is a fragment thereof, or a composition comprising the same; and instructions disclosing one or more of the dosage, administration route, administration frequency, and indications for the peptide or composition comprising the same.

[0093] The terminology used herein is intended for the purpose of describing particular embodiments only and is not intended to limit the invention. The use of terms preceded by a noun without a number does not denote a limitation of quantity, but rather indicates that there are one or more of the referenced item. The terms "including," "having," and "comprising" are to be construed as open terms (i.e., meaning "including, but not limited to").

[0094] Reciting ranges of values ​​is merely an easy way of referring to each separate value falling within the range individually, and unless expressly stated otherwise, each separate value is incorporated herein as if it were individually set forth in the specification. All range endpoints are included within the range and are independently combinable.

[0095] All methods referred to herein may be performed in any suitable manner unless otherwise specified or clearly contradicted by context. The use of any and all examples or exemplary language (e.g., "such as"), unless otherwise included in the claims, is merely to better describe the invention and does not limit the scope of the invention. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention. Unless otherwise defined, technical and scientific terms used herein have the meanings commonly understood by those skilled in the art to which the invention belongs.

[0096] The preferred embodiment of the present invention includes the best mode known to the inventors for carrying out the invention. Variations of the preferred embodiment will become apparent to those skilled in the art upon reading the foregoing description. The inventors expect that those skilled in the art will take advantage of such variations and will implement the invention in ways other than as described herein. Accordingly, this invention includes equivalents and all modifications of the subject matter recited in the appended claims as permitted by the patent laws. Furthermore, any combination of the above-described elements, within all possible variations, is encompassed by this invention unless expressly stated to the contrary herein or clearly contradicted by context. While the invention has been particularly shown and described with reference to illustrative embodiments, it will be readily apparent to those skilled in the art that various changes in form and detail can be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

[0097] Tumor necrosis factor (TNF), particularly TNF-α, is known to be released from inflammatory cells and induce a variety of cytotoxic, immune, and inflammatory responses. TNF-α is involved in the onset and prolongation of many inflammatory and autoimmune diseases, and if released into the blood and acts systemically, it can cause severe sepsis and septic shock. Because TNF-α is a factor widely involved in the immune system, active development of drugs that inhibit TNF-α is underway. TNF-α is biosynthesized in an inactive form and converted to an active form by protease cleavage. The enzyme responsible for its activation is called tumor necrosis factor-converting enzyme (TACE). Therefore, substances that inhibit TACE can treat, ameliorate, or prevent diseases, pathologies, abnormal conditions, and adverse symptoms caused by TNF-α.

[0098] High-mobility group box 1 (HMGB1) protein is present at high concentrations in the thymus, lymph nodes, testes, fetal liver, etc., and is primarily present in the nucleus of most cells, except for hepatocytes and brain cells. The HMGB1 protein has three domains: an A-box, a B-box, and a C-terminal.

[0099] The role of HMGB1 protein as an inflammation-inducing cytokine was reported by Tracey et al. in 1999. The inflammation-inducing mechanism of HMGB1 is that, upon external stimuli, HMGB1 present in the nucleus is acetylated and then translocated to the cytoplasm, where it is then secreted extracellularly or secreted from cells undergoing necrosis (Bonaldi T et al., EMBO J, (22)5551-60, 2003).

[0100] The configuration and effects of the present invention will be described in more detail below with reference to examples and experimental examples. However, the following examples and experimental examples are provided for illustrative purposes only to aid in understanding the present invention, and the scope and spirit of the present invention are not limited thereto. [Example]

[0101] Example 1: Synthesis of PEP 1 (SEQ ID NO: 163) and measurement of anti-inflammatory activity Experimental Example 1: Synthesis of PEP 1 (SEQ ID NO: 163) A peptide consisting of 16 amino acids having the following chemical structure 1 and the following sequence SEQ ID: 1 (PEP 1) selected from human telomerase was synthesized.

[0102] [ka]

[0103] The peptide PEP 1 of SEQ ID NO: 1 was prepared by a conventional solid phase peptide synthesis method. Specifically, the peptide was synthesized by coupling amino acids one by one from the C-terminus via Fmoc solid phase peptide synthesis (SPPS) using an ASP48S (Peptron, Inc., Daejeon, Republic of Korea). The peptide was used with the first amino acid at the C-terminus attached to the resin as follows. For example:

[0104] NH2-Lys(Boc)-2-chloro-Trityl Resin NH2-Ala-2-chloro-Trityl Resin NH2-Arg(Pbf)-2-chloro-Trityl Resin

[0105] All amino acid starting materials used in peptide synthesis were protected at the N-terminus with Fmoc, and the residues were protected with Trt, Boc, t-butylester (t-Bu), 2,2,4,6,7-pentamethyl dihydrobenzofuran-5-sulfonyl (Pbf), etc., all of which can be removed with acid. For example:

[0106] Fmoc-Ala-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Glu(OtBu)-OH, Fmoc-Pro-OH, Fmoc-Leu-OH, Fmoc-Ile-OH, Fmoc-Phe-OH, Fmoc-Ser(tBu)-OH, Fmoc-Thr(tBu)-OH, F moc-Lys(Boc)-OH, Fmoc-Gln(Trt)-OH, Fmoc-Trp(Boc)-OH, Fmoc-Met-OH, Fmoc-Asn(Trt)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Ahx-OH, Trt-Mercaptoaceticacid

[0107] The coupling reagents used were HBTU [2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetamethylaminium hexafluorophosphate], HOBt [N-Hydroxxybenzotriazole], and NMM [4-Methylmorpholine]. Fmoc removal was performed using 20% ​​piperidine in DMF. The synthesized peptide was separated from the resin and the protecting groups of the residues were removed using a cleavage cocktail [TFA (trifluoroacetic acid) / TIS (triisopropylsilane) / EDT (ethanedithiol) / HO = 92.5 / 2.5 / 2.5 / 2.5].

[0108] Each peptide was synthesized by repeatedly reacting the starting amino acids with protecting groups bound to the solid support, washing with solvent, and deprotecting the amino acids. The synthesized peptides were cleaved from the resin, purified by HPLC, and freeze-dried after confirming their integrity by MS.

[0109] The specific synthesis process of PEP 1 is as follows. 1) Coupling An amino acid (8 equivalents) protected by NH2-Lys(Boc)-2-chloro-Trityl Resin and coupling reagents HBTU (8 equivalents), HOBt (8 equivalents), and NMM (16 equivalents) were dissolved in DMF and added, and the mixture was reacted at room temperature for 2 hours. The mixture was then washed with DMF, MeOH, and DMF, in that order.

[0110] 2) Fmoc deprotection 20% piperidine in DMF was added, and the mixture was reacted twice for 5 minutes at room temperature, and then washed with DMF, MeOH, and DMF in that order.

[0111] 3) Reactions 1 and 2 were repeated to produce the peptide backbone NH2-E(OtBu)-AR(Pbf)-PALLT(tBu)-S(tBu)-R(Pbf)LR(Pbf)-FIPK(Boc)-2-chloro-Trityl Resin.

[0112] 4) Cleavage: After synthesis, a cleavage cocktail was added to the peptide resin, and the peptide was separated from the resin.

[0113] 5) Cooling diethyl ether is added to the resulting mixture, which is then centrifuged to precipitate the resulting peptide.

[0114] 6) After purification by Prep-HPLC, the molecular weight was confirmed by LC / MS, and the product was frozen and made into powder.

[0115] Experimental Example 2: Measurement of the anti-inflammatory activity of PEP 1 Cell line culture Raw 264.7 macrophage cells (KCBL, 40071) provided by the Korean Cell Line Bank were cultured at 1 × 10 cells / well in Dulbecco's modified Eagle's medium (DMEM; PAA, Austria) supplemented with 10% fetal bovine serum (FBS; Gibco Laboratories) and 100 units / mL of streptomycin and penicillin (Gibco Laboratories). 6 After adjusting the concentration to cells / ml, the cells were seeded into a 96-well plate and incubated at 37°C, 5% CO 2 The mixture was pre-cultured under the conditions

[0116] The next day, the medium was removed and replaced with fresh medium. 5 μg / mL of the peptide sample obtained in Experiment 1 was added to the cells. After 30 minutes of incubation in a CO2 incubator, 50 μL of medium containing LPS (final concentration 1 μg / mL) was added and the cells were incubated in an incubator (5% CO2, 37°C) for 24 hours. The inflammatory response model was treated with 1 μg / mL lipopolysaccharide (LPS; Sigma, USA) per well, while the control group was treated with phosphate-buffered saline (PBS; pH 7.2). The cell culture medium from the LPS-treated model and control group was stored in Eppendorf tubes for further analysis.

[0117] Experiment 2-1. Nitric oxide (NO) analysis Nitric oxide was measured using Raw 264.7 cells (1 × 10 6 Measurements were performed using the Griess reagent system (Promega, USA) at 100 μM (cells / ml). 50 μL of culture medium was added to a 96-well plate, and equal volumes of Griess Reaction Solution I (naphthylethylenediamide (NED) solution) and Griess Reaction Solution II (sulfanilamide solution) were mixed and added. After a 10-minute incubation, optical density was measured at 540 nm within 30 minutes using a microplate reader (Molecular Devices, USA). Nitric oxide (NO) concentrations were calculated using a sodium nitrite standard curve (0–100 μM).

[0118] As shown in Table 3 below, LPS increased NO production, but simultaneous treatment with LPS and the peptide PEP 1 reduced NO production. In particular, treatment with PEP 1 reduced the amount of NO produced during inflammation induction by 65%, indicating that inflammation induction was suppressed.

[0119] [Table 8]

[0120] Experiment 2-2. Analysis of cytokine production suppression effect To investigate the inhibitory effect of PEP 1 on inflammatory cytokine production, RAW 264.7 cells were first treated with human telomerase-derived PEP at a concentration of 15 μg / mL, followed by LPS at a concentration of 1 μg / mL and cultured for 24 hours. Supernatant samples containing the cell culture medium were collected and analyzed for cytokine levels using an ELISA kit (eBioscience, San Diego, CA).

[0121] A 96-well plate was coated with 100 μl of capture antibodies (dissolved in coating buffer at the concentration recommended by the manufacturer's protocol) and incubated overnight at 4°C. After washing the plate five times, 200 μl of assay diluents was added to each well and incubated for 1 hour at room temperature during blocking. After washing each well five times with wash buffer, cell culture medium samples or cytokine standard protein samples were diluted and added in 100 μl portions to each well. The sample-containing plate was incubated overnight at 4°C. After washing the plate five times with wash buffer, 100 μl of secondary antibody and avidin conjugate was added and incubated for 1 hour at room temperature.

[0122] After incubation with the secondary antibody, the plate was washed five times and incubated with 100 μl of avidin-HRP (BD Bioscience) for 30 minutes at room temperature. After washing the plate seven times, 100 μl of TMB solution (Pierce) was added and incubated for 15 minutes at room temperature. The reaction was terminated by adding 50 μl of 2N sulfuric acid (H2SO4) to each well. Optical density was measured at 450 nm using a microplate reader. Statistical analysis was performed using the ANOVA procedure in the SPSS program, with significance between analyses verified using Duncan's multiple range test.

[0123] Experiment 2-3: IL-6 secretion measurement As shown in Table 4 below, LPS increased the secretion of the cytokine IL-6 (interleukin-6), but simultaneous treatment with LPS and PEP 1 reduced the secretion of the inflammation-related cytokine IL-6. In particular, treatment with PEP 1 reduced the secretion of inflammation-related cytokines by more than 70%, demonstrating excellent anti-inflammatory activity.

[0124] [Table 9]

[0125] Experiment 2-4: Measurement of the inhibitory effect on HMGB1, TNF-α, and COX-2 expression Protein expression was analyzed by Western blot analysis. Cells grown in medium containing human telomerase-derived peptides were washed with PBS, treated with 0.05% trypsin-EDTA, and then collected by centrifugation. The collected cells were lysed in an appropriate volume of lysis buffer, and the intracellular debris was separated. Equal amounts of protein were separated by SDS-polyacrylamide gel electrophoresis. The separated proteins were transferred to a nitrocellulose membrane (Schleicher and Schuell, Keene, NH, USA) and reacted with specific antibodies and secondary antibodies. After application of ECL (enhanced chemiluminescence) solution (Amersham Life Science Corp., Arlington Heights, IL, USA), the membrane was exposed to X-ray film and analyzed for protein expression.

[0126] To confirm the relationship between TNF-α, which is a mechanism for inhibiting NO production, and COX-2 protein, expression levels were measured via Western blot. As shown in Table 5 below, LPS increased the expression of cytokines HMGB1, TNF-α, and COX, but simultaneous treatment with LPS and PEP 1 reduced the expression levels of inflammation-related proteins. In particular, treatment with PEP 1 of the present invention reduced the expression levels of inflammation-related cytokine proteins by more than 70%, demonstrating excellent anti-inflammatory activity.

[0127] [Table 10]

[0128] Example 2: Measurement of TNF-α inhibitory activity of PEPRIA series peptides (SEQ ID NO: 1 to SEQ ID NO: 161) In Example 1, the TNF-α inhibitory activity of the peptide of SEQ ID NO: 1 (PEP 1) was confirmed, and based on that, an experiment was carried out to confirm the TNF-α inhibitory activity of the peptides of SEQ ID NO: 1 to 161. The peptides of SEQ ID NO: 1 to 161 were synthesized using the same method as the method for synthesizing the peptide of SEQ ID NO: 1 described in Example 1, but with different attached amino acids.

[0129] Experiment 1: Cell culture After blood collection (50 ml) from healthy volunteers, peripheral blood mononuclear cells (PBMCs) were collected using Biocoll Separating Solution (Biochrom AG, Berlin, Germany). The collected PBMCs were enriched in RPMI 1640 medium supplemented with human serum (20%), transferred to a 100 mm polystyrene cell culture plate coated with human serum for 30 minutes, and cultured for 2 hours at 37°C in a 5% CO2 incubator. Subsequently, monocytes attached to the bottom were detached with cold PBS and then plated at 1 × 10 cells per well in a 96-well plate. 5To obtain cells, the cells were enriched in RPMI 1640 medium (supplemented with penicillin-streptomycin; 100 mg / ml, human serum; 20%) and cultured the day before the experiment.

[0130] Experiment 2: TNF-α inhibitory activity assay To investigate the effect of the peptides in the PEP RIA series on TNF-α, an ELISA experiment was performed. PBMC-derived monocytes were plated in a 96-well plate at 1 × 10 per well. 5 To achieve this, the cells were cultured the day before the experiment, then treated with lipopolysaccharide (LPS; 10 ng / ml, Sigma) for 2 hours and washed three times with PBS. After washing three times with PBS, the cells were starved for 1 hour in OPTI-MEM medium, treated with 4 μM peptide, and cultured for 2 hours. Three negative control groups were used: the first group was untreated; the second group was treated with estrogen (estradiol); and the third group was treated with LPS (10 ng / ml) or LPS (10 ng / ml) and estrogen (20 nM). PEP 1, which has been confirmed to have TNF-α inhibitory activity, was used as a positive control to measure TNF-α inhibitory activity. After incubation, the cell culture medium was collected and TNF-α was quantified using an ELISA kit (R&D, Minneapolis, MN, USA) according to the kit manual. The specific method for quantification is as described in Experiment 2-2 of Example 1.

[0131] Through the above experiments, peptides that affect TNF-α levels were screened. PBMC-derived monocytes were stimulated with the endotoxin LPS (10 ng / ml) for 2 hours, starved in OPTI-MEM for 1 hour, and then incubated with 161 peptides at a concentration of 4 μM for 2 hours. After incubation, TNF-α levels in the cell culture medium were measured by ELISA, and peptides that reduced TNF-α levels compared to negative and positive controls were screened (Figures 1 to 16). Compared to a comparison group treated with LPS only, the following peptides were selected as showing TNF-α inhibitory effects: SEQ ID NO: 1 to 6, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 14 to 21, SEQ ID NO: 23 to 37, SEQ ID NO: 39 to 44, SEQ ID NO: 47 to 53, SEQ ID NO: 55 to 61, SEQ ID NO: 63 to 82, SEQ ID NO: 84 to 94, SEQ ID NO: 96, SEQ ID NO: 99 to 104, SEQ ID NO: 107 to 109, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 120 to 122, SEQ ID NO: 124, SEQ ID NO: 129 to 133, SEQ ID NO: 142 to 144, SEQ ID NO: 146, SEQ ID NO: 148, SEQ ID NO: 149, and SEQ ID NO: 155 to 159.

[0132] Furthermore, the following peptides were selected as exhibiting a TNF-α inhibitory effect compared to LPS+estrogen: SEQ ID NOs: 15 to 18, 23 to 27, 29, 31 to 34, 39 to 41, 47, 48, 51 to 53, 55 to 58, 61, 65 to 68, 70, 73 to 79, 81, 82, 84 to 87, 89 to 94, 96, 99, 101 to 104, 107 to 109, 120, 121, 129 to 132, 142 to 144, 146, 148, 149, and 156 to 159.

[0133] Experiment 3: Analysis of peptides affecting TNF-α levels in THP1 cell line The experiment was carried out using THP-1 cells (American Type Culture Collection (ATCC), Manassas, VA, USA), a human acute monocytic leukemia cell line.

[0134] THP-1 was added to a 96-well plate at 1 x 10 per well. 5 The cells were enriched in RPMI 1640 medium and cultured for 4 hours. At this time, THP-1 cells were treated with 100 nM PMA (phorbol 12-myristate 13-acetate) to differentiate into macrophages. After PMA differentiation, THP-1 cells were treated with LPS for 2 hours and washed. Then, they were starved for 1 hour and then treated with PEP1 for 1 hour.

[0135] THP-1 cells differentiated with PMA were stimulated with the endotoxin LPS (10 ng / ml, Sigma) for 2 hours, washed twice with PBS, starved in OPTI-MEM for 1 hour, and then incubated with 161 peptides at a concentration of 1 μM for 1 hour. After incubation, TNF-α levels in the cell culture medium were measured by ELISA, and peptides that reduced TNF-α levels compared to the control group were screened (Figures 17-35).

[0136] As a result, peptides SEQ ID NO:1 to 5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:15, SEQ ID NO:17 to 27, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:32 to 53, SEQ ID NO:55 to 60, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:70, SEQ ID NO:72 to 82, SEQ ID NO:84 to 92, SEQ ID NO:94, SEQ ID NO:99 to 112, SEQ ID NO:114, SEQ ID NO:127 to 144, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:151, and SEQ ID NO:153 to 161 appeared to reduce TNF-α compared to the control group treated with LPS only. In addition, SEQ ID NOs: 1 to 5, 7, 9, 10, 12, 13, 15, 17 to 23, 25 to 27, 29, 30, 33 to 43, 156, 157 and 159 were selected as peptides that reduce the expression level of TNF-α compared to the group treated with LPS and estrogen.

[0137] Example 3: Analysis of inflammatory responses induced by beta-amyloid HMGB1 protein is known to function as an inflammatory cytokine by being acetylated in the nucleus in response to external stimuli, translocating to the cytoplasm, and then secreting it to the extracellular space. Because HMGB1 protein is secreted to the extracellular space when inflammation is present, the serum of patients with inflammatory diseases such as Churg-Strauss syndrome, rheumatoid arthritis, and Sjögren's syndrome contains significantly higher amounts of HMGB1 protein than normal individuals. Therefore, regardless of the type of inflammation-inducing stimulus, if the amount of HMGB1 protein in the cell nucleus is high, it means that HMGB1 protein is not secreted to the extracellular space, and therefore inflammation is considered to be suppressed.

[0138] Experiment 1. Cell Culture Undifferentiated PC12 cells (ATCC, Rockville, MD, USA) were maintained in ogarithmic-phase growth in RPMI 1640 medium containing 10% heat-inactivated horse serum, 5% heat-inactivated fetal bovine serum, 100 units / ml penicillin, and 100 μg / ml streptomycin, using pre-coated 100 mm dishes (Corning, PA, USA) coated with poly-l-lysine (Sigma, Saint Louis, MO, USA). Cultures were grown at 37°C, 5% CO2, and 50% confluence in Ca-free Hank's balanced salt solution containing 1 mM EDTA. 2+ / Mg 2+ The cells were extracted from 100 mm dishes at 1x10 6 After dividing into 1000 cells, the cells were cultured for one day. For neural differentiation, PC12 cells were serum-starved for 12 hours (RPMI 1640 medium containing 100 units / ml penicillin and 100 μg / ml streptomycin, without horse serum or fetal bovine serum), thus maintaining PC12 cells in serum-free conditions. After two days, the previous medium was replaced with fresh medium. On the third day, NGF (50 ng / ml, Sigma, Saint Louis, MO, USA) was added to the medium, and the cells were maintained in serum-free conditions for another three days. After cell differentiation, nPC cells were cultured for 48 hours with various concentrations of peptides and 20 μM beta-amyloid protein.

[0139] Experimental Example 2: Western Blot Analysis HMGB1 levels were analyzed using Western blot. 6Cells were washed twice with cold PBS and incubated on ice for 10 min in lysis buffer [50 mM Tris (pH 8.0), 150 mM NaCl, 0.02% sodium azide, 0.2% SDS, 10 μg / ml phenylmethylsulfonyl fluoride (PMSF), 50 μM / ml aprotinin, 1% Igep 630, 100 mM NaF, 0.5% sodium deoxycholate, 0.5 mM EDTA, 0.1 mM EGTA]. Intact cells and nuclei were centrifuged at 2,000 x g for 10 min, and lysates were removed at 10,000 x g. Anti-HMGB1 (1:1000; Cell Signaling, Beverly, MA, USA) and anti-β-tubulin (1:1000; Cell Signaling, Beverly, MA, USA) antibodies were used. Cell membranes were washed with Tris-buffered saline containing 0.05% Tween-20 (TBST) and detected with ECL (Amersham Pharmacia Biotech) followed by processing with an HRP-conjugated anti-rabbit antibody (Amersham Pharmacia Biotech, Piscataway, NJ, USA). Blots were quantified using an image analyzer (GE Healthcare, Image Quant LAS 4000).

[0140] Figures 36 to 108 show selected peptides that demonstrate intracellular HMGB1 accumulation based on the results of Western blot analysis. Protein expression levels were confirmed using tubulins shown in the figures, and the sequences of the selected peptides are as follows: SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:52, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:52, SEQ ID NO:57, SEQ ID NO:60, SEQ ID NO:61 , SEQ ID NO:62, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:91, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:104, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO:109, SEQ ID NO:111, SEQ ID NO:112, SEQ ID NO:115, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:122, SEQ ID NO:124, SEQ ID NO:125, SEQ ID NO:126, SEQ ID NO:129, SEQ ID NO:130, SEQ ID NO:131, SEQ ID NO:132, SEQ ID NO:135, SEQ ID NO:146, SEQ ID NO:151, SEQ ID NO:154 and SEQ ID NO:156.

Claims

1. A peptide having anti-inflammatory activity, the peptide consisting of (a) an amino acid sequence selected from the group consisting of SEQ ID NOs: 129, 71, and 72, or (b) an amino acid sequence having at least 90% sequence identity with the amino acid sequence set forth in (a).

2. The peptide of claim 1 , which is derived from human telomerase.

3. A polynucleotide encoding the peptide of claim 1.

4. (a) an amino acid sequence selected from the group consisting of SEQ ID NOs: 129, 71, and 72; or (b) an amino acid sequence having at least 90% sequence identity with the amino acid sequence defined in (a); An anti-inflammatory composition comprising as an active ingredient a peptide consisting of:

5. The anti-inflammatory composition of claim 4 , wherein the peptide consists of the amino acid sequence of SEQ ID NO: 129, 71, or 72.

6. The anti-inflammatory composition according to claim 4, which is a cosmetic composition for improving or preventing skin inflammation.

7. The anti-inflammatory composition according to claim 4, which is a pharmaceutical composition for treating or preventing an inflammatory disease.

8. The anti-inflammatory composition according to claim 4, which is a food composition for treating or preventing inflammation.

9. The composition according to any one of claims 4 to 8; and instructions including at least one of the dosage, route of administration, frequency of administration, and indication for the composition; A kit for treating or preventing an inflammatory disease, comprising:

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