title: Activation of inducible nitric oxide synthase gene in murine macrophages requires protein phosphatases 1 and 2A activities.
abstract: The purpose of these studies was to identify phosphatase activities required for the production of nitric oxide in murine macrophages exposed to lipopolysaccharide (LPS), synthetic lipopeptide (LPP), and mouse interferon-gamma (IFN-gamma). The in vitro treatment of macrophages with IFN-gamma and LPS or IFN-gamma and LPP resulted in production of NO, which was inhibited by addition of the specific phosphatase 1 and 2A (PP1/2A) inhibitors okadaic acid (OA), calyculin A, and cantharidin (but not the nonactive analogues okadaic acid tetraacetate and 1,4-dimethylendothall). OA suppressed the accumulation of steady-state inducible NO synthase (iNOS) mRNA and iNOS protein (without alteration of their stability). The cytosol and nuclei of control macrophages contained large amounts of PP1/2A activities that were inhibited by OA in a dose-dependent manner. Taken together, these data indicate that PP1/2A activities are involved in the regulation of iNOS gene expression in murine macrophages.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000502:physiology*; D054645:Protein Phosphatase 1; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1