M. Yamashita et al., INDUCTION OF NITRIC-OXIDE SYNTHASE BY LIPOPOLYSACCHARIDE AND ITS INHIBITION BY AURANOFIN IN RAW-264.7 CELLS, European journal of pharmacology, 338(2), 1997, pp. 151-158
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.