INHIBITION OF NITRIC-OXIDE (NO-ASTERISK) PRODUCTION IN MURINE MACROPHAGES BY FLAVONES

The effect of flavone (2-phenylbenzopyran-4-one) and three amino-subst ituted flavones on the production of nitrite by murine activated perit oneal macrophages was studied in vitro. Activated peritoneal macrophag es obtained from mice pre-treated with concanavalin A (Con A) (in vivo ), after exposure in vitro to lipopolysaccharide (LPS) at a concentrat ion of 100 ng/ml, produced nitrite (20.3 +/- 2.5 nmol/10(6) cells), as measured after 24 hr by the Griess reaction. Stimulation of productio n of nitrite was inhibited by N-G-monomethyl-l-arginine, suggesting th at nitrite was formed via nitric oxide (NO.) as a product of metabolis m of arginine. Stimulation was inhibited by flavone and the aminoflavo nes (20-100 mu M). 3'-amino-4'-hydroxyflavone was the most potent inhi bitor of nitrite production. Genistein ydroxy-3-(4-hydroxy-phenyl)-4H- 1-benzopyran-4-one) also inhibited production of nitrite, by a mechani sm that appears not to involve protein tyrosine kinases. These results suggest that the flavones can modulate the immune responses and the i nflammatory reactions by controlling production of nitric oxide.