Anti-CXCL9, anti-CXCL 10, anti-CXCL 11, anti-CXCL 13, anti-CXCR3 and anti-CXCR5 agents for inflammatory disorder

An inflammatory disease, CCR5 technology, applied in anti-inflammatory agents, disease diagnosis, metabolic diseases, etc., can solve the problem that the exact mechanism of chemokine-mediated events is not clear

Inactive Publication Date: 2015-08-26
JYANT TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the precise mechanism of chemokine-mediated events remains unclear

Method used

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  • Anti-CXCL9, anti-CXCL 10, anti-CXCL 11, anti-CXCL 13, anti-CXCR3 and anti-CXCR5 agents for inflammatory disorder
  • Anti-CXCL9, anti-CXCL 10, anti-CXCL 11, anti-CXCL 13, anti-CXCR3 and anti-CXCR5 agents for inflammatory disorder
  • Anti-CXCL9, anti-CXCL 10, anti-CXCL 11, anti-CXCL 13, anti-CXCR3 and anti-CXCR5 agents for inflammatory disorder

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0225] Example 1: Upregulation of chemokines and their receptors in inflammatory diseases

[0226] Materials and methods

[0227]The protein sequences of the chemokines used herein are recorded in NIH-NCBI GenBank as follows: (1) CXCR1 (ACCESSION #NP 000625), (2) CXCR2 (ACCESSION #NP 001548), (3) CXCL1 (ACCESSION #NP001502), (4) CXCL2 (ACCESSION#NP 002080), (5) CXCL3 (ACCESSION#NP 002081), (6) CXCL5 (ACCESSION#NP002985), (7) CXCL6 (ACCESSION#NP 002984), (8) CXCL7 (ACCESSION# NP 002695), (9) CXCL8 (IL-8, ACCESSION#NP 000575), (10) CXCR4 (ACCESSION#NP 003458), (11) CXCL12 (ACCESSION#NP 000600), (12) CXCR5A (ACCESSION#NP 116743 ), (13) CXCR5B (ACCESSION#NP001707), (14) CXCL13 (ACCESSION#NP 006410), (15) CXCR6 (ACCESSION#NP 006555), (16) CXCL16 (ACCESSION#NP 071342), (17) CCL16 ( ACCESSION#NP 004581), (18)CCL25(ACCESSION#NP_005616.2), (19)CCL25-1(ACCESSION#NP 005615), (20)CCL25-2(ACCESSION#NP683686), (21)CX3CR1(ACCESSION# NP 001328) and (22) CX3CL1 (ACCESSION #NP 002987).

...

Embodiment 2

[0245] Embodiment 2: IFN-γ, CXCL10, MIG, I-TAC, CXCR3 in murine animals mRNA expression in colitis

[0246] figure 1 The mRNA expression of IFN-γ, CXCL10, MIG, I-TAC and CXCR3 during murine colitis is shown. IL-10 reared from cages with a C57BL / 6 background - / -Mice were removed from the laminar flow barrier to naturally develop colitis. After sacrifice, total RNA was isolated from the colon or mesenteric lymph nodes of mice before the onset of colitis (sterile conditions, blank rectangular bars) and after colitis onset (filled rectangular bars). IFN-γ, IP-10, MIG, I-TAC and CXCR3 mRNA expression levels were determined following RT-PCT analysis capable of detecting greater than 20 copies of transcribed cDNA. exist figure 1 In, the Log of the transcript 10 Copies are expressed relative to the true copy of 18S rRNA.

[0247] Such as figure 1 showed that IL-10 in patients with colitis - / - Significant increases in CXCR3 and CXCL10 expression were observed in the inflame...

Embodiment 3

[0248] Example 3: Reception of CD45RB by adoptive transfer HI or CXCR3 + CD4 + T thin TCRβxδ - / - Histological analysis of IBD in mice

[0249] figure 2 Shows acceptance of CD45RB by adoptive transfer HI or CXCR3 + CD4 + TCRβxδ of T cells - / - Histological analysis of IBD in mice. CD45RB received from normal C57BL / 6 mice Lo - (Panel A), CD45RB Hi - (Panel B) or CXCR3 + -CD4 + TCRβxδ of T cells (Panel C) - / - 60X magnification of enteritis in mice. Transverse sections of the intestine showed differences in wall thickness, enlargement of the mucosal layer, crypt deformation, and leukocyte infiltration using hematoxylin-eosin stained 6 μm paraffin sections.

[0250] This analysis revealed that CXCR3, both composed of the CD45RB population, + CD4 + T cells in TCRβxδ - / - Induction of colitis was induced in mice (Panel C)

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Abstract

A method for detecting an inflammatory disease in a subject is disclosed. The method comprises the steps of (a) detecting a level of expression of one or more inflammatory disease markers in a biological sample obtained from the subject; and (b) comparing the level of expression of said one or more inflammatory disease markers in the biological sample to a normal level of expression of the one or more inflammatory disease markers, wherein the one or more inflammatory disease markers comprise one or more markers selected from the group consisting of CXCL9, CXCLIO, CXCLl 1, CXCLl 3, CXCR3 and CXCR5. Also disclosed are a method for monitoring the course of treatment for an inflammatory disease in a subject and a kit for detecting an inflammatory disease in a subject.

Description

technical field [0001] This application mainly relates to the detection of inflammatory diseases. More specifically, the present application relates to methods for detecting inflammatory diseases using anti-chemokine and / or anti-chemokine receptor detection reagents. Background technique [0002] Despite recent advances in research related to inflammatory processes, methods for diagnosing and treating chronic inflammatory diseases remain largely unknown. This may be because the factors that initiate and maintain the inflammatory state in the host are many and complex. Current treatments have disadvantages associated with them, including suppression of the immune system which may render the host more susceptible to bacterial, viral and parasitic infections. For example, the use of steroids is a traditional approach in the treatment of chronic inflammation. This treatment may lead to suppression of protective immunity and changes in body weight. Advances in biotechnology h...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K48/00A61K38/17A61P29/00A61P3/10
CPCG01N2800/52C07K16/24G01N2333/7158A61K2039/505G01N33/6893C07K2317/76A61P3/10A61P29/00
Inventor 詹姆斯·W·利拉德
Owner JYANT TECH
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