Abstract
Prostaglandins have been shown to have a wide range of effects on nitric oxide synthesis when studied in different cell populations. The proximity of hepatocytes to eicosanoid-producing endothelial cells and Kupffer cells prompted us to determine the effects of PGE2 and LTB4 on hepatocyte NO production by the inducible nitric oxide synthase (iNOS, NOS-2) in vitro. PGE2 decreased hepatocyte NO synthesis in a concentration-dependent manner when the cells were stimulated with a combination of cytokines or IL-1 alone. LTB4 had a similar effect. PGE2 had to be present at the time of cytokine exposure to produce maximal inhibition of NO synthesis. Reduced synthesis of NO2- was associated with reduced NOS-2 mRNA levels suggesting that the induction of NOS-2 was inhibited. These findings demonstrate that eicosanoids can regulate hepatocyte NO synthesis in vitro.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Blotting, Northern
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Cytokines / pharmacology*
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Dinoprostone / pharmacology*
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Dose-Response Relationship, Drug
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Gene Expression Regulation, Enzymologic / drug effects*
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Gene Expression Regulation, Enzymologic / genetics
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Interferons / pharmacology
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Interleukin-1 / pharmacology
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Leukotriene B4 / pharmacology*
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Lipopolysaccharides / pharmacology
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Liver / cytology
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Liver / drug effects
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Liver / enzymology*
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Male
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Nitric Oxide / biosynthesis
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitric Oxide Synthase / biosynthesis*
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Nitric Oxide Synthase / genetics
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RNA, Messenger / analysis
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RNA, Messenger / genetics
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Rats
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Rats, Sprague-Dawley
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Time Factors
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Cytokines
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Interleukin-1
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Lipopolysaccharides
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RNA, Messenger
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Tumor Necrosis Factor-alpha
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Leukotriene B4
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Nitric Oxide
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Interferons
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Nitric Oxide Synthase
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Dinoprostone