INDUCTION OF NITRIC-OXIDE SYNTHASE BY LIPOPOLYSACCHARIDE AND ITS INHIBITION BY AURANOFIN IN RAW-264.7 CELLS

In RAW 264.7 cells, a murine macrophage cell line, treatment with lipo polysaccharide (1 to 10 ng/ml) stimulated production of nitric oxide ( NO), which was inhibited by L-N-G-monomethyl-L-arginine acetate, an in hibitor of NO synthase. Auranofin, an orally active chrysotherapeutic agent, also inhibited the lipopolysaccharide-induced NO production in a concentration-dependent manner (0.3 to 3 mu M). Other gold salts suc h as aurothioglucose and aurothiomalate had no effect. Western blot an alysis demonstrated that the lipopolysaccharide (10 ng/ml)-induced exp ression of inducible NO synthase protein was inhibited by auranofin as well as by the protein synthesis inhibitor cycloheximide. In addition , the lipopolysaccharide-induced increase in the level of mRNA for ind ucible NO synthase was also lowered by auranofin. Furthermore, auranof in showed no direct effect on the conversion of [H-3]arginine to [3H]c itrulline by the cell lysate. These findings indicate that auranofin i nhibits lipopolysaccharide-induced NO production by suppressing the ex pression of inducible NO synthase. (C) 1997 Elsevier Science B.V.