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

Authors

  • Kerstin Koerber,

    1. Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen
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    • K.K. and G.S. contributed equally to this work.

  • Gabriele Sass,

    1. Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen
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    • K.K. and G.S. contributed equally to this work.

  • Alexandra K. Kiemer,

    1. Department of Pharmacy, Center of Drug Research, Pharmaceutical Biology, University of Munich, Munich, Germany
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  • Angelika M. Vollmar,

    1. Department of Pharmacy, Center of Drug Research, Pharmaceutical Biology, University of Munich, Munich, Germany
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  • Gisa Tiegs

    Corresponding author
    1. Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Erlangen
    • Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nuremberg, Fahrstrasse 17, D-91054 Erlangen, Germany. fax: (49) 9131-85 22 774.
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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)-α and/or interferon (IFN)-γ, two mediators of con A–induced liver injury, the TNF receptor (TNFR) usage leading to iNOS expression, and its connection with nuclear factor κB (NF-κB) activation. In conclusion, iNOS expression in vivo is dependent on both TNF-α and IFN-γ. Although con A–induced liver injury depends on both TNFR1 and TNFR2, TNF-dependent iNOS expression is mediated exclusively by TNFR1 and requires NF-κB activation.

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