The level of nitrite accumulation in the culture media of astrocytes activated with lipopolysaccharide (LPS) and interferon-gamma (IFN) was decreased by pretreatment of cells with LY294002, a quercetin derivative developed for phosphatidylinositol-3-kinase (PI3K) inhibitor, in a dose-dependent manner. The expression of iNOS mRNA in the astrocytes was inhibited by LY294002, as revealed by reverse transcriptional polymerase chain reaction and agarose gel electrophoresis. The catalytic activity of astrocytic iNOS was also inhibited by LY294002. On the other hand, wortmannin which was known to enhance endotoxin-induced NO production in macrophages by inhibiting PI3K did not cause any significant change in the NO production and iNOS mRNA expression of the astrocytes. These results suggest that LY294002 suppresses NO production in the astrocytes through not only the inhibition of iNOS mRNA expression but also the inhibition of the iNOS activity and that PI3K is not involved in the inhibitory actions of LY294002.pc 1999 Academic Press@p$hr
Copyright 1999 Academic Press.