Induction of COX-2 expression by nitric oxide in rheumatoid synovial cells

Prostaglandins formed by cyclooxygenase (COX) enzymes are important mediato rs of inflammation. The contribution of inducible COX-2 in the rheumatoid s ynovium is well documented. In this study, we evaluated the contribution of nitric oxide (NO) to COX-2 expression in rheumatoid synovial cells. Exposu re of rheumatoid synovial cells to a NO donor, SNAP, induced COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated th at COX-2 mRNA was induced in SNAP-treated synovial cells. Dexamethasone at therapeutic concentrations markedly inhibited this NO-mediated COX-2 expres sion in synovial cells. In contrast to its effect on COX-2 expression, SNAP did not affect the constitutive expression of COX-1 in rheumatoid synovial cells. Our findings suggest that NO is an important modulator of COX-2 exp ression and that glucocorticoids exert their anti-inflammatory action in rh eumatoid synovium, at least in part, by suppression of COX-2 induction. (C) 2000 Academic Press.