PROSTAGLANDIN E(2), REGULATES INDUCIBLE NITRIC-OXIDE SYNTHASE IN THE MURINE MACROPHAGE CELL-LINE J774

We have evaluated the role of prostaglandin E(2) (PGE(2)) in the synth esis of nitric oxide (NO) by the activation of the inducible form of n itric oxide synthase (NOS) in the murine macrophage cell line, J774, s timulated with different doses of lipopolysaccharide (LPS). The stimul ation of the J774 line with suboptimal doses of LPS (0.1 mu g/mL) caus ed a production of endogenous PGE(2) that was capable of stimulating N OS activity inducing an increase in the NO synthesis, as attested by t he fact that cyclooxygenase enzyme inhibitor, indomethacin, significan tly reduced NO secretion. On the contrary, a higher dose of LPS (I mu g/mL) produced high levels of PGE(2) that reduced the levels of NOS an d, subsequently, NO production. Experiments carried out with exogenous PGE(2) indicated that concentrations between 1 and 10 ng/mL are able to stimulate the expression of NOS and the release of NO, while higher concentrations (>50 ng/mL) are inhibitory. Furthermore, our data indi cate that there is a network of interaction which involves NO, PGE(2), and tumor necrosis factor. High levels of PGE(2) inhibited TNF alpha secretion, which in turn could exert inhibitory effects on NO synthesi s.