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CYP2E1- and TNFalpha/LPS-Induced Oxidative Stress and MAPK Signaling Pathways in Alcoholic Liver Disease

  • Cytokines That Affect Liver Fibrosis and Activation of Hepatic Myofibroblasts (Tatiana Kisseleva, Section Editor)
  • Published:
Current Pathobiology Reports

Abstract

CYP2E1-induced oxidative stress plays a central role in the development and progression of alcohol-induced liver injury. Ethanol-induced intestinal hyperpermeability and endotoxemia with activation of Kupffer cells and production of cytokines such as TNFα also play a key role in ethanol liver injury. This review discusses studies in mice as to how oxidant stress from ethanol or pyrazole induction of CYP2E1 sensitizes the liver to the toxicity of TNFα and LPS and that activation of mitogen-activated protein kinases JNK and p38 MAPK plays a role in this potentiated hepatotoxicity. Thus, two independent risk factors believed to be important for alcohol liver injury, namely ethanol induction of CYP2E1 and ethanol-elevation of TNFα, interact with each other to promote liver injury.

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Acknowledgments

Studies in the author’s lab were supported by Grants from the National Institute on Alcohol Abuse and Alcoholism, NIH.

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  1. Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA

    Arthur I. Cederbaum

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  1. Arthur I. Cederbaum
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Correspondence to Arthur I. Cederbaum.

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This article is part of the Topical Collection on Cytokines That Affect Liver Fibrosis and Activation of Hepatic Myofibroblasts.

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Cederbaum, A.I. CYP2E1- and TNFalpha/LPS-Induced Oxidative Stress and MAPK Signaling Pathways in Alcoholic Liver Disease. Curr Pathobiol Rep 3, 263–272 (2015). https://doi.org/10.1007/s40139-015-0092-0

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  • DOI: https://doi.org/10.1007/s40139-015-0092-0

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