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The Role of IL-17 Signaling in Regulation of the Liver–Brain Axis and Intestinal Permeability in Alcoholic Liver Disease

  • Cytokines that affect liver fibrosis and activation of hepatic myofibroblasts ( T.Kisseleva, Section Editor)
  • Published:
Current Pathobiology Reports

Abstract

Alcoholic liver disease (ALD) progresses from a normal liver, to steatosis, steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). Despite intensive studies, the pathogenesis of ALD is poorly understood, in part due to a lack of suitable animal models which mimic the stages of ALD progression. Furthermore, the role of IL-17 in ALD has not been evaluated. We and others have recently demonstrated that IL-17 signaling plays a critical role in the development of liver fibrosis and cancer. Here we summarize the most recent evidence supporting the role of IL-17 in ALD. As a result of a collaborative effort of Drs. Karin, Gao, Tsukamoto, and Kisseleva, we developed several improved models of ALD in mice: (1) chronic-plus-binge model that mimics early stages of steatohepatitis, (2) intragastric ethanol feeding model that mimics alcoholic steatohepatitis and fibrosis, and (3) diethylnitrosamine (DEN) + alcohol model that mimics alcoholic liver cancer. These models might provide new insights into the mechanism of IL-17 signaling in ALD and help identify novel therapeutic targets.

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Abbreviations

Col:

Collagen α1(I)

α-SMA:

α-Smooth muscle actin

qHSCs:

Quiescent hepatic stellate cells

aHSCs:

Activated hepatic stellate cells

iHSCs:

Inactivated hepatic stellate cells

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Acknowledgments

Supported by the National Institutes of Health (DK088837, U01AA022614, AI0777802 P50 AA011999).

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Authors and Affiliations

  1. Department of Medicine, UC San Diego, La Jolla, CA, USA

    Hsiao-Yen Ma, Jun Xu, Xiao Liu, Yunheng Zhu & David Brenner

  2. Department of Surgery, UC San Diego, 9500 Gilman Drive # 0702, La Jolla, CA, 92093, USA

    Hsiao-Yen Ma, Jun Xu, Xiao Liu, Yunheng Zhu & Tatiana Kisseleva

  3. Department of Pharmacology, UC San Diego, La Jolla, CA, USA

    Michael Karin

  4. Department of Psychiatry, UC San Diego, La Jolla, CA, USA

    Dilip V. Jeste & Igor Grant

  5. Department of Neurosciences, UC San Diego, La Jolla, CA, USA

    Cedric Geoffroy & Binhai Zheng

  6. Stein Institute for Research on Aging, UC San Diego, La Jolla, CA, USA

    Dilip V. Jeste

  7. Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA

    Bin Gao

  8. Southern California Research Center for ALPD & Cirrhosis, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Hidekazu Tsukamoto

  9. Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Hidekazu Tsukamoto

  10. Department of Veterans Affairs Great Los Angeles Healthcare System, Los Angeles, CA, USA

    Hidekazu Tsukamoto

  11. Department of Molecular & Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, USA

    Amanda J. Roberts

  12. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA

    Candice Contet

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  1. Hsiao-Yen Ma
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  2. Jun Xu
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  3. Xiao Liu
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  15. Tatiana Kisseleva
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Correspondence to Tatiana Kisseleva.

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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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Ma, HY., Xu, J., Liu, X. et al. The Role of IL-17 Signaling in Regulation of the Liver–Brain Axis and Intestinal Permeability in Alcoholic Liver Disease. Curr Pathobiol Rep 4, 27–35 (2016). https://doi.org/10.1007/s40139-016-0097-3

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