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Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2017; 23(17): 3043-3052
Published online May 7, 2017. doi: 10.3748/wjg.v23.i17.3043
Macrophage inflammatory protein-2 as mediator of inflammation in acute liver injury
Chao-Chao Qin, Yan-Ning Liu, Ying Hu, Ying Yang, Zhi Chen
Chao-Chao Qin, Yan-Ning Liu, Ying Hu, Ying Yang, Zhi Chen, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Chao-Chao Qin, Yan-Ning Liu, Ying Hu, Ying Yang, Zhi Chen, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
Author contributions: All authors contributed to this paper; Qin CC, Liu YN and Chen Z contributed to study conception, literature review and analysis, and drafting and critical revision of the manuscript; Hu Y and Yang Y contributed to literature review and analysis and figure drawing.
Supported by the State 12th 5-Year Plan S&T Projects of China, No. 2012ZX10002007; and National Natural Science Foundation of China, No. 81272679, No. 81470851.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest related to this study.
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: Dr. Zhi Chen, Professor, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 866 Yuhong Road, Hangzhou 310003, Zhejiang Province, China. zjuchenzhi@zju.edu.cn
Telephone: +86-571-87236579 Fax: +86-571-87068731
Received: November 1, 2016
Peer-review started: November 3, 2016
First decision: December 19, 2016
Revised: January 11, 2017
Accepted: February 8, 2017
Article in press: February 8, 2017
Published online: May 7, 2017
Processing time: 186 Days and 1.7 Hours
Abstract

Macrophage inflammatory protein (MIP)-2 is one of the CXC chemokines and is also known as chemokine CXC ligand (CXCL2). MIP-2 affects neutrophil recruitment and activation through the p38 mitogen-activated-protein-kinase-dependent signaling pathway, by binding to its specific receptors, CXCR1 and CXCR2. MIP-2 is produced by a variety of cell types, such as macrophages, monocytes, epithelial cells, and hepatocytes, in response to infection or injury. In liver injury, activated Kupffer cells are known as the major source of MIP-2. MIP-2-recruited and activated neutrophils can accelerate liver inflammation by releasing various inflammatory mediators. Here, we give a brief introduction to the basic molecular and cellular sources of MIP-2, and focus on its physiological and pathological functions in acute liver injury induced by concanavalin A, lipopolysaccharides, irradiation, ischemia/reperfusion, alcohol, and hypoxia, and hepatectomy-induced liver regeneration and tumor colorectal metastasis. Further understanding of the regulatory mechanisms of MIP-2 secretion and activation may be helpful to develop MIP-2-targeted therapeutic strategies to prevent liver inflammation.

Keywords: Macrophage inflammatory protein-2; Liver injury; Polymorphonuclear neutrophils; Macrophages; Inflammation

Core tip: Macrophage inflammatory protein (MIP)-2 is produced by a variety of cell types in response to infection or injury, and affects neutrophil recruitment and activation by binding to chemokine CXC receptor (CXCR)1 and CXCR2. MIP-2 plays a complex dual role in the development of liver diseases by mediating liver inflammation at a high concentration and promoting liver regeneration at a low concentration. Here, we review its physiological and pathological functions in various types of liver damage. Further understanding of the regulatory mechanisms of MIP-2 may be helpful to develop MIP-2-targeted therapeutic strategies.