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: Hsiao-Yen Ma, Jun Xu, Xiao Liu, Yunheng Zhu, Bin Gao, Michael Karin, Hidekazu Tsukamoto, Dilip V Jeste, Igor Grant, Amanda J Roberts, Candice Contet, Cedric Geoffroy, Binhai Zheng, David Brenner, Tatiana Kisseleva
• Journal: Current pathobiology reports (Curr Pathobiol Rep) Vol. 4 Issue 1 Pg. 27-35 (Mar 2016) ISSN: 2167-485X [Print] United States
• PMID: 27239399 (Publication Type: Journal Article)