title: The role of IL-17 signaling in regulation of the liver-brain axis and intestinal permeability in Alcoholic Liver Disease.
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 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.
authors.affiliation: Department of Medicine, UC San Diego, La Jolla, CA; Department of Surgery, UC San Diego, La Jolla, CA.
authors.forename: Hsiao-Yen
authors.initials: HY
authors.lastname: Ma
authors.affiliation: Department of Medicine, UC San Diego, La Jolla, CA; Department of Surgery, UC San Diego, La Jolla, CA.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Medicine, UC San Diego, La Jolla, CA; Department of Surgery, UC San Diego, La Jolla, CA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Medicine, UC San Diego, La Jolla, CA; Department of Surgery, UC San Diego, La Jolla, CA.
authors.forename: Yunheng
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National, Institutes of Health, Bethesda, Maryland.
authors.forename: Bin
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, UC San Diego, La Jolla, CA.
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.affiliation: Southern California Research Center for ALPD & Cirrhosis Department of Pathology Keck School of Medicine of USC, University of Southern California, and Department of Veterans Affairs Great Los Angeles Healthcare System, Los Angeles, CA.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tsukamoto
authors.affiliation: Department of Psychiatry, UC San Diego, La Jolla, CA; Stein Institute for Research on Aging, UC San Diego, La Jolla, CA.
authors.forename: Dilip V
authors.initials: DV
authors.lastname: Jeste
authors.affiliation: Department of Psychiatry, UC San Diego, La Jolla, CA.
authors.forename: Igor
authors.initials: I
authors.lastname: Grant
authors.affiliation: Department of Molecular & Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Roberts
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA.
authors.forename: Candice
authors.initials: C
authors.lastname: Contet
authors.affiliation: Department of Neurosciences, UC San Diego, La Jolla, CA.
authors.forename: Cedric
authors.initials: C
authors.lastname: Geoffroy
authors.affiliation: Department of Neurosciences, UC San Diego, La Jolla, CA.
authors.forename: Binhai
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Department of Medicine, UC San Diego, La Jolla, CA.
authors.forename: David
authors.initials: D
authors.lastname: Brenner
authors.affiliation: Department of Surgery, UC San Diego, La Jolla, CA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kisseleva
keywords: Adaptive Immunity; Cytokines; Inflammation; Innate Immunity; activated myofibroblasts; alcoholic liver disease; ethanol metabolism; hepatocellular carcinoma; regression of liver fibrosis