Abstract
In this study, we showed that nitric oxide (NO) donors induced the mesangial cell proliferation and cyclooxygenase-2 (COX-2) protein expression in murine mesangial cells. An inflammatory condition [lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma)] could also induce cell proliferation and significantly enhance inducible nitric oxide synthase (iNOS) and COX-2 expression. Phosphoinositide 3-kinase (PI3K) inhibitor, LY294002, inhibited these responses. LPS/IFN-gamma-induced COX-2 expression in mesangial cells could be inhibited by iNOS inhibitor, aminoguanidine. Selective COX-2 inhibitor, NS398, was capable of inhibiting NO donor- or LPS/IFN-gamma-induced mesangial cell proliferation. Both NO donor and LPS/IFN-gamma markedly activated the PI3K activity and the phosphorylation of Akt and nuclear factor (NF)-kappaB DNA binding activity in mesangial cells, which could be inhibited by LY294002 and transfection of dominant-negative vectors of PI3K/p85 and Akt. These results indicate that a PI3K/Akt-dependent pathway involved in the NO-regulated COX-2 expression and cell proliferation in mesangial cells under inflammatory condition.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Proliferation
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Cells, Cultured
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Chromones / pharmacology
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Cyclooxygenase 2
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Dose-Response Relationship, Drug
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Genes, Dominant
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Genetic Vectors
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Glomerular Mesangium / cytology*
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Glomerular Mesangium / pathology
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Guanidines / pharmacology
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I-kappa B Kinase
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Immunoblotting
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Inflammation
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Interferon-gamma / metabolism
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Lipopolysaccharides / metabolism
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Mice
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Morpholines / pharmacology
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NF-kappa B / metabolism
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Nitric Oxide / metabolism*
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type II
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Nitrites / metabolism
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Nitrobenzenes / pharmacology
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Phosphatidylinositol 3-Kinases / metabolism*
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Prostaglandin-Endoperoxide Synthases / biosynthesis*
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Prostaglandin-Endoperoxide Synthases / metabolism
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Protein Serine-Threonine Kinases / metabolism
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Sulfonamides / pharmacology
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Time Factors
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Transfection
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Up-Regulation
Substances
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Chromones
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Guanidines
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Lipopolysaccharides
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Morpholines
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NF-kappa B
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Nitrites
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Nitrobenzenes
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Sulfonamides
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N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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Nitric Oxide
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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Interferon-gamma
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Protein Serine-Threonine Kinases
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Chuk protein, mouse
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I-kappa B Kinase
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Ikbkb protein, mouse
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Ikbke protein, mouse
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pimagedine