PGE2 and LTB4 inhibit cytokine-stimulated nitric oxide synthase type 2 expression in isolated rat hepatocytes.
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.
Harbrecht
B G
BG
Department of Surgery, University of Pittsburgh School of Medicine, A1010 Presbyterian University Hospital, PA 15213, USA.
Kim
Y M
YM
Wirant
E M
EM
Shapiro
R A
RA
Billiar
T R
TR
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
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