Cyclooxygenase‐2: an essential regulator of NO‐mediated apoptosis

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Abstract
Lipopolysaccharide/interferon gamma up-regulated inducible nitric oxide synthase and caused nitric oxide generation and concomitant apoptotic cell death in RAW 264.7 macrophages. Exogenously supplied nitric oxide donors such as S-nitrosoglutathione produced equivalent alterations. Preactivation of macrophages with a combination of lipopolysaccharide/interferon gamma under conditions of blocked NO synthase--N(G)-monomethyl-L-arginine addition--or stimulation with a low, nondestructive dose of S-nitrosoglutathione conferred protection against high and thus apoptotic NO concentrations. Here we report that induction of cyclooxygenase-2 during the preactivation period is a critical regulator of macrophage apoptosis. Under resting conditions, macrophages do not express cyclooxygenase-2, whereas lipopolysaccharide/interferon gamma/N(G)-monomethyl-L-arginine prestimulation for 12-15 h caused protein expression. In parallel, preactivation of RAW cells with a low, nontoxic dose of S-nitrosoglutathione promoted prot...

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