The role of peroxynitrite in cyclooxygenase-2 expression of rheumatoid synovium
Migita, K.; Yamasaki, S.; Ida, H.; Kita, M.; Hida, A.; Shibatomi, K.; Kawakami, A.; Aoyagi, T.; Eguchi, K.
Clinical and Experimental Rheumatology 20(1): 59-62
2002
ISSN/ISBN: 0392-856X PMID: 11892711 Document Number: 544774
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. 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. 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.