Inhibitory effect of retinoic acid on expression of inducible nitric oxidesynthase gene in L929 cells

Inflammation has been known to be associated with excess synthesis of nitri c oxide (NO) by inducible NO synthase (iNOS). Retinoids have been reported to have anti-inflammatory activity, but the mechanism by which they can eli cit this activity is poorly understood. The effects of retinoids on NO synt hesis and iNOS gene expression in murine fibroblast L929 cells were examine d. Treatment of the cells with interferon-gamma resulted in excess NO synth esis and iNOS gene expression. All-trans-retinoic acid significantly inhibi ted NO synthesis and iNOS gene expression in a dose-dependent manner. Simil arly, 9-cis-retinoic acid also inhibited NO synthesis., but retinol did not show any inhibitory effect on NO synthesis. These findings suggest that th e modulation of iNOS gene expression is another possible pathway by which r etinoids may function as anti-inflammatory agents.