IFN-gamma-induced iNOS mRNA expression is inhibited by rebamipide in murine macrophage RAW264.7 cells

To investigate the effects of rebamipide, an antigastritis and anti-gastric ulcer drug, on inducible nitric oxide synthase (iNOS), murine macrophage RAW264.7 cells were treated with interferon-gamma (IFN-gamma) in the presence of rebamipide. NO production was stimulated by IFN-gamma, and the level was attenuated by rebamipide in a dose-dependent manner. Therefore, we investigated the possibility that either rebamipide directly inhibited iNOS enzyme activity or that it reduced iNOS mRNA expression. In a cell-free system, rebamipide did not affect iNOS enzyme activity; however, rebamipide inhibited iNOS mRNA and protein expression induced by IFN-gamma. Thus, we concluded that rebamipide inhibited IFN-gamma-induced NO production as a result of its inhibitory action on iNOS mRNA expression.