| Project/Area Number |
05807042
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
SANO Hajime Kyoto Prefectural University of Medicine First Department of Internal Medicine Assistant Professor, 医学部, 助手 (00196304)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Rheumatoid arthritis / Corticotropin-releasing hormone / Adjuvant arthritis / Streptococcal cell wall arthritis / Synovium / Lewis rats / beta-endorphin / Glucocorticoid / PCR法 |
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| Research Abstract |
We examined the role of corticotropin-releasing hormone in the pathogenesis of rheumatoid arthritis in human and rats injected with adjuvant or SCW.1) CRH protein and mRNA were expressed in RA synovia (lining cell layr, inflammatory mononuclear cells, fibroblast-like cells, blood vessels) using immunohisochemistry, PCR method and in situ hybridization. 2) The expression of CRH protein and mRNA in RA synovia was significantly increased compared to osteoarthritis (OA) synovia. 3) CRH protein was demonstrated in synovial tissues and fluids by HPLC.4) CRH was also expressed in synovium, cartilage and skin in model rats for RA (SCW or adjuvant arthritis). 5) Glucocorticoid suppressed SCW and adjuvant arthritis in Lewis rats as well as CRH expression. 6) CRH was expressed in macrophage-derived cells. 7) Injection of anti-CRH antibody in Lewis rats suppressed arthritis scores in adjuvant-induced arthritis (40-50%). 8) beta-endorphin (beta-Ep) was also expressed in synovia from patients with RA and rats with SCW-or adjuvant-induced arthritis. 10) CRH and beta-Ep were coexpressed in synovial lining cell layr.
These data suggest ; 1) CRH is produced by synovial cells in arthritic joints, 2) CRH induces beta-Ep in synovial cells, 3) CRH functions as a local mediator of inflammatory arthritis, 4) CRH may play a role in the pathogenesis of RA.
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