Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin.
Andreas K. Nussler,M. Di Silvio,Timothy R. Billiar,Rosemary A. Hoffman,David A. Geller,Rick Selby,Juan Madariaga,Richard L. Simmons +7 more
TLDR
Evidence is provided for the existence of typical inducible NO biosynthesis in a human cell type after stimulation with interleukin 1, tumor necrosis factor, IFN- gamma, and endotoxin in freshly isolated human hepatocytes.Abstract:
Nitric oxide (NO) is a short-lived biologic mediator that is shown to be induced in various cell types and to cause many metabolic changes in target cells. Inhibition of tumor cell growth and antimicrobial activity has been attributed to the stimulation of the inducible type of the NO synthase (NOS). However, there is limited evidence for the existence of such inducible NOS in a human cell type. We show here the induction of NO biosynthesis in freshly isolated human hepatocytes (HC) after stimulation with interleukin 1, tumor necrosis factor (TNF), IFN-gamma, and endotoxin. Increased levels of nitrite (NO2-) and nitrate (NO3-) in culture supernatants were associated with NADPH-dependent NOS activity in the cell lysates. The production of NO2- and NO3- was inhibited by NG-monomethyl L-arginine and was associated with an increase in cyclic guanylate monophosphate release. The data presented here provide evidence for the existence of typical inducible NO biosynthesis in a human cell type.read more
Citations
More filters
Journal ArticleDOI
The L-Arginine-Nitric Oxide Pathway
Salvador Moncada,Annie Higgs +1 more
TL;DR: The discovery that mammalian cells generate nitric oxide, a gas previously considered to be merely an atmospheric pollutant, is providing important information about many biologic processes.
Journal ArticleDOI
Nitric oxide as a secretory product of mammalian cells.
TL;DR: How different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule is reviewed.
Journal ArticleDOI
Mechanisms of Hepatic Fibrogenesis
TL;DR: Clinical and translational implications of these advances have become clear, and have begun to impact significantly on the management and outlook of patients with chronic liver disease.
Journal ArticleDOI
Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon gamma and bacterial lipopolysaccharide.
TL;DR: In this article, a 1,749-bp fragment from the 5'-flanking region of the iNOS gene was cloned from a mouse genomic library, and used S1 nuclease mapping and primer extension to identify the mRNA transcription start site within it.
Journal ArticleDOI
Nitric oxide: A physiologic messenger
TL;DR: A noxious, unstable gas, nitric oxide, a byproduct of automobile exhaust, electric power stations, and lightning, was discovered in the body, where it participates in various functions, including suppression of pathogens, vasodilation, and neurotransmission, focusing on its clinical relevance.
References
More filters
Journal ArticleDOI
Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.
TL;DR: The vascular effects of EDRF released from perfused bovine intrapulmonary artery and vein were compared with the effects of NO delivered by superfusion over endothelium-denuded arterial and venous strips arranged in a cascade to determine whether nitric oxide (NO) is responsible for the vascular smooth muscle relaxation elicited by endothelia-derived relaxing factor (EDRF).
Journal ArticleDOI
Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum
David S. Bredt,Solomon H. Snyder +1 more
TL;DR: It is established that nitric oxide mediates the stimulation by glutamate of cGMP formation, which mediates influences of numerous neurotransmitters and modulators on vascular smooth muscle and leukocytes.
Journal ArticleDOI
Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man.
TL;DR: Results indicate that the dilator action of endothelium-derived NO contributes to the control of basal and stimulated regional blood flow in man.
Journal ArticleDOI
Role of nitric oxide synthesis in macrophage antimicrobial activity.
TL;DR: It is suggested that synthesis of NO mediates much of the antimicrobial activity of mouse macrophages against some fungal, helminthic, protozoal and bacterial pathogens.
Journal ArticleDOI
Endogenous nitric oxide inhibits human platelet adhesion to vascular endothelium.
TL;DR: It is suggested that the effect of bradykinin is mediated by the release of nitric oxide from the endothelial cells, and thatNitric oxide release contributes to the non-adhesive properties of vascular endothelium.