Ee. Aeberhard et al., NONSTEROIDAL ANTIINFLAMMATORY DRUGS INHIBIT EXPRESSION OF THE INDUCIBLE NITRIC-OXIDE SYNTHASE GENE, Biochemical and biophysical research communications, 208(3), 1995, pp. 1053-1059
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.