Concurrent generation of nitric oxide and superoxide inhibits proteoglycan synthesis in bovine articular chondrocytes : involvement of peroxynitrite 軟骨細胞におけるIL-1によるperoxynitriteの誘導とその作用

博士論文

[ABSTRACT] Objective. Nitric oxide (NO), widely assumed to be a mediator of interleukin 1 (IL-1), inhibits proteoglycan synthesis in articular chondrocytes. IL-1 also produces superoxide anion. We hypothesized that the IL-1 inhibited proteoglycan synthesis is the result of peroxynitrite formed by the reaction of NO with superoxide. Methods. Bovine articular chondrocytes were cultured in the presence of SIN-1, which leads to simultaneous generation of both NO and superoxide. Proteoglycan synthesis was measured based on the incorporation of 133S1su lfate, and the presence of peroxynitrite was confirmed using immunohistochemistry. Results. SIN-1 inhibited proteoglycan synthesis and superoxide dismutase reversed SIN-1 inhibited proteoglycan synthesis, indicating the simultaneous generation of superoxide is essential to inhibit proteoglycan synthesis. IL-1 induced peroxynitrite in articular chondrocytes and addition of peroxynitrite inhibited proteoglycan synthesis. Conclusion. The concurrent generation of superoxide anion and NO is required for the action of IL-1 to inhibit proteoglycan synthesis. Peroxynitrite is a candidate for this underlying mechanism. Rheumatol 1998;25:2169-74)

学位の種類：医学　　学位授与年月日：1999/3/23　指導： 田中, 清介 教授(Director: Prof. Tanaka, Seisuke)　　報告番号：甲第477号　　学内授与番号：医627　　NDL書誌ID：000000335677

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