In vivo regulation of inducible no synthase in immune-mediated liver injury in mice

Kerstin Koerber; Gabriele Sass; Alexandra K Kiemer; Angelika M Vollmar; Gisa Tiegs

doi:10.1053/jhep.2002.36155

In vivo regulation of inducible no synthase in immune-mediated liver injury in mice

Hepatology. 2002 Nov;36(5):1061-9. doi: 10.1053/jhep.2002.36155.

Authors

Kerstin Koerber¹, Gabriele Sass, Alexandra K Kiemer, Angelika M Vollmar, Gisa Tiegs

Affiliation

¹ Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Germany.

PMID: 12395315
DOI: 10.1053/jhep.2002.36155

Abstract

Inducible nitric oxide synthase (iNOS) has been shown to play an important role in the development of liver injury. iNOS deficiency protects mice from hemorrhage/resuscitation as well as from cytokine-mediated liver injury, for example, after administration of concanavalin A (con A). Here we investigated the in vivo effects of tumor necrosis factor (TNF)-alpha and/or interferon (IFN)-gamma, two mediators of con A-induced liver injury, the TNF receptor (TNFR) usage leading to iNOS expression, and its connection with nuclear factor kappaB (NF-kappaB) activation. In conclusion, iNOS expression in vivo is dependent on both TNF-alpha and IFN-gamma. Although con A-induced liver injury depends on both TNFR1 and TNFR2, TNF-dependent iNOS expression is mediated exclusively by TNFR1 and requires NF-kappaB activation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies / pharmacology
Antigens, CD / immunology
Antigens, CD / metabolism
Chemical and Drug Induced Liver Injury
Concanavalin A
Gene Expression Regulation, Enzymologic / immunology
Interferon-gamma / immunology
Interferon-gamma / metabolism
Liver Diseases / enzymology*
Liver Diseases / immunology*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
NF-kappa B / metabolism
Nitric Oxide Synthase / genetics*
Nitric Oxide Synthase / immunology*
Nitric Oxide Synthase / metabolism
Nitric Oxide Synthase Type II
Receptors, Tumor Necrosis Factor / immunology
Receptors, Tumor Necrosis Factor / metabolism
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Signal Transduction / immunology
Tumor Necrosis Factor-alpha / immunology
Tumor Necrosis Factor-alpha / metabolism

Substances

Antibodies
Antigens, CD
NF-kappa B
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Tumor Necrosis Factor-alpha
Concanavalin A
Interferon-gamma
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nos2 protein, mouse