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We have evaluated the role of prostaglandin E₂ (PGE₂) in the synthesis of nitric oxide (NO) by the activation of the inducible form of nitric oxide synthase (NOS) in the murine macrophage cell line, J774, stimulated with different doses of lipopolysaccharide (LPS). The stimulation of the J774 line with suboptimal doses of LPS (0.1 μg/mL) caused a production of endogenous PGE₂ that was capable of stimulating NOS activity inducing an increase in the NO synthesis, as attested by the fact that cyclooxygenase enzyme inhibitor, indomethacin, significantly reduced NO secretion. On the contrary, a higher dose of LPS (1 μg/mL) produced high levels of PGE₂ that reduced the levels of NOS and, subsequently, NO production. Experiments carried out with exogenous PGE₂ 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 …