| Project/Area Number |
07670536
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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 | 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) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Rheumatoid arthritis / Corticotropin-releasing hormone / beta-endorphin / neuropeptides / Synovium / Alzet pump / Adjuvant arthritis / Hypothalamic-pituitary-adrenal axis dysfunction / アジュバンド関節炎 / corticotropin-releasing hormone / 抗血清 |
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| Research Abstract |
We examined hypothalamic-pituitary-adrenal (HPA) axis dysfunction in the pathogenesis of rheumatoid arthritis in human and adjuvant or SCW arthritis in rats.
1) CRH and beta-endorphin were expressed in RA synovia (lining cell layr, inflammatory mononuclear cells, fibroblast-like cells, blood vessels) using immunohistochemistry, PCR method and in situ hybridization. 2) The expression of CRH and beta-endorphin in RA synovia was significantly increased compared to osteoarthritis (OA) synovia. 3) CRH mRNA was also expressed in lining cell layr, inflammatory mononuclear cells, fibroblast-like cells and blood vessels of RA patients 4) CRH and beta-endorphin were 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 and beta-endorphin expression. 6) Injection of anti-CRH antibody or anti-beta-endorphin suppressed arthritis scores in adjuvant-induced Lewis rats (40-50%). 7) Anti-CRH antibody or anti-beta-endorphin suppressed CRH and beta-endorphin in synovium and cartilage.
These data suggest ; 1) CRH and beta-endorphin function as a local mediator of inflammatory arthritis, 2) CRH and beta-endorphin play a role in the pathogenesis of RA.3) Antibodies against CRH and beta-endorphin may be used for therapy of RA.
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