The effect of nitric oxide on cytokine-induced release of PGE(2) by human cultured astroglial cells

2 Incubation of T 67 astroglial cell line with IL-beta (10 ng ml(-1)) and TNF-alpha (500 u ml(-1)) produced a significant (P < 0.05) increase of both nitrite (the breakdown product of NO), cyclic GMP and PGE(2) levels in cell supernatants. N-omega-nitro-L-arginine methyl ester (L-NAME; 20-300 mu M), an inhibitor of NO synthase (NOS), inhibited the increase of cyclic GMP and nitrite levels found in supernatants of cytokine-treated astroglial cells and reduced the release of PGE(2). The latter effect showed that the enhanced arachidonic acid (AA) metabolism subsequent to stimulation of astroglial cells with IL-1 beta and TNF-alpha was, at least in part, induced by NO. This occurred also when sodium nitroprusside (SNP; 120 mu M), an NO donor, was incubated with astroglial cells, an effect antagonized by oxyhaemoglobin (OxyHb; 10 mu M).