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.