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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 28, 2016; 22(4): 1348-1356
Published online Jan 28, 2016. doi: 10.3748/wjg.v22.i4.1348
Hepatic non-parenchymal cells: Master regulators of alcoholic liver disease?
Wonhyo Seo, Won-Il Jeong
Wonhyo Seo, Won-Il Jeong, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-338, South Korea
Author contributions: Seo W and Jeong WI wrote the manuscript and contributed equally to this work.
Supported by A grant from the Next-Generation BioGreen 21 Program, No. PJ009957; Rural Development Administration; and partially from the Korea Advanced Institute of Science and Technology Institute for the BioCentury, South Korea.
Conflict-of-interest statement: The authors have no conflict of interest to report.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Won-Il Jeong, DVM, PhD, Associate Professor, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 373-1 Yuseong-gu, Daejeon 305-338, South Korea. wijeong@kaist.ac.kr
Telephone: +82-42-3504239 Fax: +82-42-3504240
Received: June 26, 2015
Peer-review started: June 27, 2015
First decision: September 9, 2015
Revised: September 28, 2015
Accepted: December 12, 2015
Article in press: December 14, 2015
Published online: January 28, 2016
Processing time: 208 Days and 0.8 Hours
Abstract

Chronic alcohol consumption is one of the most common causes of the progression of alcoholic liver disease (ALD). In the past, alcohol-mediated hepatocyte injury was assumed to be a significantly major cause of ALD. However, a huge number of recent and brilliant studies have demonstrated that hepatic non-parenchymal cells including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells and diverse types of lymphocytes play crucial roles in the pathogenesis of ALD by producing inflammatory mediators such as cytokines, oxidative stress, microRNA, and lipid-originated metabolites (retinoic acid and endocannabinoids) or by directly interacting with parenchymal cells (hepatocytes). Therefore, understanding the comprehensive roles of hepatic non-parenchymal cells during the development of ALD will provide new integrative directions for the treatment of ALD. This review will address the roles of non-parenchymal cells in alcoholic steatosis, inflammation, and liver fibrosis and might help us to discover possible therapeutic targets and treatments involving modulating the non-parenchymal cells in ALD.

Keywords: Alcoholic liver disease; Reactive oxygen stress; Endocannabinoid; NADPH oxidase

Core tip: Chronic alcohol consumption commonly causes chronic liver diseases including liver fibrosis and cirrhosis. According to recent studies, hepatic non-parenchymal cells including Kupffer cells, hepatic stellate cells, liver sinusoidal endothelial cells and liver lymphocytes are important to modulate the pathogenesis of alcoholic liver disease (ALD) by producing inflammatory mediators or by interacting either hepatic parenchymal cells (hepatocytes) or non-parenchymal cells. Therefore, understanding the novel roles of hepatic non-parenchymal cells during the development of ALD is important and it will be considered as therapeutic targets for alcoholic liver diseases.