NONSTEROIDAL ANTIINFLAMMATORY DRUGS INHIBIT EXPRESSION OF THE INDUCIBLE NITRIC-OXIDE SYNTHASE GENE

Increased nitric oxide production is associated with acute and chronic inflammatory processes. Accordingly, we tested the hypothesis that th e therapeutic action of nonsteroidal anti-inflammatory drugs could be attributed at least in part to inhibition of excess nitric oxide produ ction. We report here that sodium salicylate, aspirin, ibuprofen, and indomethacin markedly inhibited the appearance of the inducible inflam matory nitric oxide synthase in rat alveolar macrophages activated wit h lipopolysaccharide and interferon gamma. We attribute the mechanism of nitric oxide synthase inhibition by nonsteroidal anti-inflammatory drugs to pretranslational control of enzyme expression and not to dire ct inhibition of enzymatic activity. These observations indicate that the chronic anti-inflammatory action of nonsteroidal anti-inflammatory drugs may be due not only to inhibition of prostaglandin synthesis bu t also to inhibition of inducible nitric oxide synthase gene expressio n and nitric oxide synthesis. (C) 1995 Academic Press, Inc.