Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 7, 2015; 21(5): 1424-1435
Published online Feb 7, 2015. doi: 10.3748/wjg.v21.i5.1424
High-mobility group box 1 protein and its role in severe acute pancreatitis
Xiao Shen, Wei-Qin Li
Xiao Shen, Wei-Qin Li, Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, China
Author contributions: Shen X searched the database and wrote the manuscript; Li WQ revised the manuscript.
Supported by National Science Foundation of China, No. 81170438; and grant from Jiangsu Provincial Special Program of Medical Science, No. BL2012006.
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: Wei-Qin Li, MD, PhD, Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing 210002, Jiangsu Province, China. njzy_pancrea@163.com
Telephone: +86-25-84803956 Fax: +86-25-84803956
Received: August 16, 2014
Peer-review started: August 16, 2014
First decision: September 15, 2014
Revised: October 7, 2014
Accepted: November 11, 2014
Article in press: November 11, 2014
Published online: February 7, 2015
Abstract

The high mobility group box 1 (HMGB1), which belongs to the subfamily of HMG-1/-2, is a highly conserved single peptide chain consisting of 215 amino acid residues with a molecular weight of approximately 24894 Da. HMGB1 is a ubiquitous nuclear protein in mammals and plays a vital role in inflammatory diseases. Acute pancreatitis is one of the most common causes of acute abdominal pain with a poor prognosis. Acute pancreatitis is an acute inflammatory process of the pancreas (duration of less than six months), for which the severe form is called severe acute pancreatitis (SAP). More and more studies have shown that HMGB1 has a bidirectional effect in the pathogenesis of SAP. Extracellular HMGB1 can aggravate the pancreatic inflammatory process, whereas intracellular HMGB1 has a protective effect against pancreatitis. The mechanism of HMGB1 is multiple, mainly through the nuclear factor-κB pathway. Receptors for advanced glycation end-products and toll-like receptors (TLR), especially TLR-2 and TLR-4, are two major types of receptors mediating the inflammatory process triggered by HMGB1 and may be also the main mediators in the pathogenesis of SAP. HMGB1 inhibitors, such as ethyl pyruvate, pyrrolidine dithiocarbamate and Scolopendra subspinipes mutilans, can decrease the level of extracellular HMGB1 and are the promising targets in the treatment of SAP.

Keywords: High mobility group box 1 protein, Inhibitors, Inflammation, Severe acute pancreatitis, Nuclear factor kappa B

Core tip: The newly discovered high mobility group box 1 protein is a ubiquitous nuclear protein that exists extensively in mammals. More and more studies have shown its vital role in inflammation. This paper is the first to reveal the bidirectional effect of this protein in the pathogenesis of severe acute pancreatitis and its role as a potential treatment target.