High mobility box 1 mediates neutrophil recruitment in myocardial ischemia-reperfusion injury through toll like receptor 4-related pathway |
| |
Authors: | Hua-Sheng Ding Jun Yang Fei-Li Gong Jian Yang Jia-Wang Ding Song Li Yu-Rong Jiang |
| |
Institution: | Institute of Cardiovascular Diseases, China Three Gorges University; Department of Cardiology, The First College of Clinical Medical Sciences, China Three Gorges University, 443000 Yichang, Hubei Province, China. |
| |
Abstract: | 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 30min of ischemia and 6h 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. |
| |
Keywords: | HMGB1 high mobility box 1 TLR-4 Toll-like receptor 4 I/R ischemia/reperfusion MPO myeloperoxidase TNF-a tumor necrosis factor α IL-8 interleukin-8 PCR polymerase chain reaction ELISA enzyme-linked immunosorbent assay NF-κB nuclear factor kappa B LAD left anterior descending coronary artery JNKs c-JunN-terminal kinases RAGE receptor for advanced glycation end products IOD the total size of positive area × average optical density of the total positive area |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|