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The role of peroxynitrite in cyclooxygenase-2 expression of rheumatoid synovium
1First Department of Internal Medicine, Nagasaki University School of Medicine, Japan. migita@net.nagasaki-u.ac.jp
Objective:
Reactive oxygen intermediates play an important role in the inflammatory processes of rheumatoid arthritis. Cyclooxygenase-2 is an inducible form of an enzyme involved in prostanoid biosynthesis. This study linked peroxynitrite (ONOO-) to the signaling pathways that induce COX-2.
Results:
Exposure of rheumatoid synovial cells to peroxynitrite resulted in COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated that COX-2 mRNA was induced in peroxynitrite-treated rheumatoid synovial cells. Dexamethasone markedly inhibited this peroxynitrite-mediated COX-2 expression at therapeutic concentrations.
Conclusion:
This study demonstrates that oxidant stress is an important inducer of COX-2 in rheumatoid synovium. This induction may contribute to the amplification of prostanoids in the rheumatoid inflammatory process.
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