title: PGE2 and LTB4 inhibit cytokine-stimulated nitric oxide synthase type 2 expression in isolated rat hepatocytes.
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.
authors.affiliation: Department of Surgery, University of Pittsburgh School of Medicine, A1010 Presbyterian University Hospital, PA 15213, USA.
authors.forename: B G
authors.initials: BG
authors.lastname: Harbrecht
authors.forename: Y M
authors.initials: YM
authors.lastname: Kim
authors.forename: E M
authors.initials: EM
authors.lastname: Wirant
authors.forename: R A
authors.initials: RA
authors.lastname: Shapiro
authors.forename: T R
authors.initials: TR
authors.lastname: Billiar
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D016207:Cytokines / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000235:genetics; D007372:Interferons / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007375:Interleukin-1; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007975:Leukotriene B4; D009569:Nitric Oxide; D007372:Interferons; D019001:Nitric Oxide Synthase; D015232:Dinoprostone