Differential regulation of constitutive and inducible nitric oxide production by inflammatory stimuli in murine endothelial cells.
The murine vascular endothelial cell line send1 expresses both constitutive and inducible nitric oxide (NO) synthases. Interferon-gamma (IFN gamma) or endotoxin (LPS) alone inhibited constitutive NO production in a dose and time dependent manner. Addition of L-arginine had no influence on the decrease of NO production caused by IFN gamma or LPS. On the other hand, IFN gamma and LPS synergized in the induction of high output NO production. Successive incubations with IFN gamma and LPS in different sequences revealed IFN gamma as the time setting signal for the induction of NO synthesis. These results demonstrate that LPS and IFN gamma have a direct suppressive effect on constitutive NO synthase while at the same time they strongly activate inducible NO production. Thus inflammatory stimuli trigger murine vascular endothelial cells to switch from constitutive to inducible NO synthase activity.
Department of Medicine, University Hospital of Zürich, Switzerland.
R
R
Walter
A
A
Schaffner
G
G
Schoedon
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology*; D007371:Interferon-gamma / Q000494:pharmacology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D011994:Recombinant Proteins; D013997:Time Factors
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D009569:Nitric Oxide; D007371:Interferon-gamma