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.
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1 July 1992
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July 01 1992
Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin.
A K Nussler,
A K Nussler
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
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M Di Silvio,
M Di Silvio
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
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T R Billiar,
T R Billiar
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
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R A Hoffman,
R A Hoffman
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
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D A Geller,
D A Geller
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
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R Selby,
R Selby
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
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J Madariaga,
J Madariaga
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
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R L Simmons
R L Simmons
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
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A K Nussler
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
M Di Silvio
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
T R Billiar
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
R A Hoffman
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
D A Geller
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
R Selby
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
J Madariaga
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
R L Simmons
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1992) 176 (1): 261–264.
Citation
A K Nussler, M Di Silvio, T R Billiar, R A Hoffman, D A Geller, R Selby, J Madariaga, R L Simmons; Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin.. J Exp Med 1 July 1992; 176 (1): 261–264. doi: https://doi.org/10.1084/jem.176.1.261
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