2003 Fiscal Year Final Research Report Summary
Study on the mechanism for the production of CXCR3-agonisitic chemokines by synovial fibroblasts from patients with rheumatoid arthritis
| Project/Area Number |
14570413
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | OKAYAMA UNIVERSITY |
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Principal Investigator |
YAMAMURA Masahiro Okayama University, Graduate School of Medicine and Dentistry, Associate Professor, 大学院・医歯学総合研究科, 助教授 (80252956)
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| Co-Investigator(Kenkyū-buntansha) |
MAESHIMA Youhei Okayama University, Hospitals, Assistant, 医学部・歯学部附属病院, 助手 (10343287)
WADA Jun Okayama University, Graduate School of Medicine and Dentistry, Assistant, 大学院・医歯学総合研究科, 助手 (30294408)
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| Project Period (FY) |
2002 – 2003
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| Keywords | rheumatoid arthritis / Th1-immune response / synovial fibroblasts / CXCL9 (Mig) / CXCL10 (IP-10) / CXCL11 (1-TAC) / interferon-γ (IFN-γ) / tumor necrosis factor-α (TNF-α) |
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| Research Abstract |
The inflamed synovial tissue of rheumatoid arthritis (RA) is characterized by an infiltration with Th1 cells that predominantly express the chemokine receptors CXCR3 and CCRS. In this study, we investigated the production of the CXCR3 agonistic chemokines CXCL9, CXCL10, and CXCL11 by synovial tissue cells and synovial fibroblast-cell lines (forth or fifth passage) from RA patients. Concentrations of all CXCR3 ligands in synovial fluids were markedly higher in RA patients than in osteoarthritis (OA) patients. Synovial tissue cells from RA patients more strongly expressed mRNAs for CXCR3 ligands and spontaneously secreted larger amounts of these chemokine proteins, compared with the cells from OA patients. The mRNA expression of all CXCR3 ligands was induced in synovial fibroblasts from RA patients after stimulation with interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), or interleukin-1β (IL-1β). However, synovial fibroblasts significantly secreted CXCL9 and CXCL10 proteins, but not CXCL11 protein, after IFN-γ stimulation, and secreted only CXCL10 protein after TNF-α or IL-1β stimulation. When stimulated with a combination of IFN-γ and TNF-α, these cells were able to secrete large amounts of all three chemokines. These results indicate that synovial fibroblasts may be involved in perpetuating the Th1 immune response by producing the Th1-associated chemokines CXCR3 ligands, and the synergistic effect of IFN-γ and TNF-α may be important for their chemokine production in RA joints.
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Research Products
(9 results)
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[Publications] Bleharski JR, Li H, Meinken C, Graeber TG, Ochoa M-T, Yamamura M, Burdick A, Sarno EN, Wagner M, Rollinghoff M, Rea TH, Colonna M, Stenger S, Bloom BR, Eisenberg D, Modlin RL: "Use of genomic profiling in leprosy to discriminate clinical forms of the disease."Science. 301(5639). 1527-1530 (2003)
Description
「研究成果報告書概要(欧文)」より
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