| Project/Area Number |
11670088
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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 |
General pharmacology
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| Research Institution | Shimane Medical University |
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Principal Investigator |
KOBAYASHI Yuta Shimane Medical University Department of Pharmacology, Associate Professor, 医学部, 助教授 (40162028)
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| Co-Investigator(Kenkyū-buntansha) |
OKUNISHI Hideki Shimane Medical University Department of Pharmacology, Professor, 医学部, 教授 (70111888)
柿添 栄一 島根医科大学, 医学部, 助手 (40252910)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | rheum atoid arthritis / mast cells / collagen-induced arthritis mice / cromolyn sodium / synovium / Matrix Metalloproteinase / Cytokines / コラーゲン誘発関節炎 / マウス / 中医薬 / Matriix Metalloproteinase / インターロイキン6 |
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| Research Abstract |
To clarify the role of mast cells (MCs) in pathological process of bovine type II collagen (CII)-induced arthritis (CIA) of male DBA/1J mice, which is a model for rheumatoid arthritis, effects of 2 kinds of oral deliverable prodrug of cromolyn sodium were examined. The prodrugs were applied to CII-immunized mice for 7 or 8 weeks, starting after the apparent occurrence of CIA in week 6 after the first immunization. Both drugs were applied once a day. Symptomatic scores of arthritis elevated significantly in non-treated immunized mice, and the elevation of scores was inhibited by prodrugs-treatment. Radiographic scores or phalangeal destruction were also improved by the prodrugs. Pathohistological observation and serum IgG type anti-CII antibody titers measurement also indicated improvement by the prodrugs. Serum interleukin 6 was higher in non-treated immunized mice, and the elevation was inhibited by a prodrug-treatment. MCs number in arthritic or corresponding region was increased in non-treated immunized mice and the increase was reduced by the prodrugs-treatment. Then, the effects of a prodrug on matrix metalloproteinase (MMP)-2, -3 and -9 expression by immunohistochemistry in finger joints of CIA mice were investigated. The extent and intensity of immunostaining of MMP-2, -3 and -9 was dramatically suppressed in synovium, cartilage and cartilage-pannus junction. In conclusion, orally applied prodrugs of a MC stabilizer have an efficacy on rheumatoid arthritis model. Significant correlation of MCs numbers and arthritis symptoms as well as effects of the prodrugs suggests the significant role of MCs in the pathogenesis of arthritis.
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