High mobility box 1 mediates neutrophil recruitment in myocardial ischemia-reperfusion injury through toll like receptor 4-related pathway

被引：41

作者：

Ding, Hua-Sheng ^{[1
]}

Yang, Jun ^{[1
]}

Gong, Fei-Li ^{[2
]}

Yang, Jian ^{[1
]}

Ding, Jia-Wang ^{[1
]}

Li, Song ^{[1
]}

Jiang, Yu-Rong ^{[1
]}

机构：

[1] China Three Gorges Univ, Coll Clin Med Sci 1, Dept Cardiol, Inst Cardiovasc Dis, Yichang 443000, Hubei Province, Peoples R China

[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Immunol, Wuhan 430030, Hubei Province, Peoples R China

来源：

GENE | 2012年 / 509卷 / 01期

基金：

中国国家自然科学基金;

关键词：

High mobility group box-1; Neutrophil recruitment; Myocardial ischemia-reperfusion injury; Toll-like receptor 4; Interleukin-8; INFLAMMATORY RESPONSE; PROTEIN HMGB1; DYSFUNCTION; ACTIVATION; EXPRESSION; INFARCTION; CLONING; CELLS; GENE; TIME;

D O I：

10.1016/j.gene.2012.07.072

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

This study aimed to explore the role of high mobility box 1 (HMGB1) and its receptor toll like receptor 4 (TLR4) on neutrophils in myocardial ischemia reperfusion (I/R) injury. We constructed TLR4-mutant (C3H/HeJ) and control (C3H/HeN) mouse models of myocardial I/R injury and subjected the mice to 30 min of ischemia and 6 h of reperfusion. Light microscope was used to observe structural changes in the myocardium. HMGB1 levels were measured using quantitative real-time PCR and immunohistochemistry. Neutrophil accumulation, TNF-a expression and IL-8 levels were analyzed via myeloperoxidase (MPO) biochemical studies, quantitative real-time PCR and ELISA, respectively. The results demonstrated that fewer neutrophils infiltrated in the myocardium of TLR4-mutant mice after myocardial I/R and that TLR4 deficiency markedly decreased the ischemic injury caused by ischemia/reperfusion, and inhibited the expression of HMGB1, TNF-a, and IL-8, all of which were up-regulated by ischemia/reperfusion. These findings suggest that HMGB1 plays a central role in recruiting neutrophils during myocardial I/R leading to worsened myocardial I/R injury. This recruitment mechanism is possibly due to its inflammatory and chemokine functions based on the TLR4-dependent pathway. Crown Copyright (C) 2012 Published by Elsevier B.V. All rights reserved.

引用

页码：149 / 153

页数：5

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