s-nitro-n-acetylpenicillamine and Osteoarthritis

Prostaglandins formed by cyclooxygenase (COX) enzymes are important mediators of inflammation. The contribution of inducible COX-2 in the rheumatoid synovium is well documented. In this study, we evaluated the contribution of nitric oxide (NO) to COX-2 expression in rheumatoid synovial cells. Exposure of rheumatoid synovial cells to a NO donor, SNAP, induced COX-2 protein expression in a dose-dependent manner. RT-PCR analysis also demonstrated that COX-2 mRNA was induced in SNAP-treated synovial cells. Dexamethasone at therapeutic concentrations markedly inhibited this NO-mediated COX-2 expression 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 expression and that glucocorticoids exert their anti-inflammatory action in rheumatoid synovium, at least in part, by suppression of COX-2 induction.

Topics: Arthritis, Rheumatoid; Base Sequence; Cells, Cultured; Cyclooxygenase 2; DNA Primers; Enzyme Induction; Gene Expression; Humans; Isoenzymes; Membrane Proteins; Nitric Oxide; Nitric Oxide Donors; Osteoarthritis; Penicillamine; Prostaglandin-Endoperoxide Synthases; RNA, Messenger; Synovial Membrane