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

Overview

Journal Curr Pathobiol Rep

Specialty Pathology

Date 2016 May 31

PMID 27239399

Citations 16

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

Affiliations

Soon will be listed here.

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.

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