Extracellular heat-shock protein 70 aggravates cerulein-induced pancreatitis through toll-like receptor-4 in mice  

作　　者：SONG Jun-min LIU Hong-xiang LI Yuan ZENG Yu-jian ZHOU Zong-guang LIU Hai-yi XU Bing WANG Ling ZHOU Bin WANG Rong 

机构地区：[1]Department of General Surgery Ⅲ and Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China [2]Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China

出　　处：《Chinese Medical Journal》2008年第15期1420-1425,共6页中华医学杂志（英文版）

基　　金：This study was supported by grants from the National Natural Science Foundation of China （No. 30400434 and No. 30571811） and China Medical Board （No. 96636 ）.

摘　　要：Background In patients suffering from acute pancreatitis, the pathogenesis is not completely understood, and several recent studies in vitro suggested that heat shock proteins might play an important role in cell signaling. To investigate the possible role of extracellular heat shock protein 70 （Hsp70） in pancreatitis, toll-like receptor-4 （TLR4）-deficient and wild-type mice were administered with exogenous Hsp70 during the course of cerulein-induced pancreatitis （CIP）. Methods Acute pancreatitis was induced by 5 intraperitoneal injections of cerulein at hourly intervals, and then treated with recombinant Hsp70 through the caudal vein 4 hours after the start of cerulein injections. Subsequently serum amylase and serum cytokines levels were detected. Histologic alteration of the pancreas was evaluated. Tumor necrosis factor alpha （TNF-α） concentrations and myeloperoxidase （MPO） activity in both pancreas and lungs were analyzed. The nuclear factor kappa B （NF-κB） activation in pancreatic tissue was measured using a sensitive RelA enzyme-linked immunosorbent assay. Results Treatment with recombinant Hsp70 to wild-type mice in CIP resulted in significant aggravation of inflammation in pancreas, elevated levels of serum cytokines, up-regulation of pulmonary MPO activity and increase of lung tissues TNF-α concentrations. In contrast, treatment with Hsp70 to TLR4-deficient mice had little effect on serum cytokines levels pancreatic inflammation, pulmonary MPO activity and TNF-α concentrations. Conclusions The results suggest that extracellular Hsp70 might induce systemic inflammatory response syndrome （SlRS）-Iike response in vivo and TLR4 might be involved in the Hsp70-mediated activation of inflammatory reaction in the progression of CIP without infection.Background In patients suffering from acute pancreatitis, the pathogenesis is not completely understood, and several recent studies in vitro suggested that heat shock proteins might play an important role in cell signaling. To investigate the possible role of extracellular heat shock protein 70 （Hsp70） in pancreatitis, toll-like receptor-4 （TLR4）-deficient and wild-type mice were administered with exogenous Hsp70 during the course of cerulein-induced pancreatitis （CIP）. Methods Acute pancreatitis was induced by 5 intraperitoneal injections of cerulein at hourly intervals, and then treated with recombinant Hsp70 through the caudal vein 4 hours after the start of cerulein injections. Subsequently serum amylase and serum cytokines levels were detected. Histologic alteration of the pancreas was evaluated. Tumor necrosis factor alpha （TNF-α） concentrations and myeloperoxidase （MPO） activity in both pancreas and lungs were analyzed. The nuclear factor kappa B （NF-κB） activation in pancreatic tissue was measured using a sensitive RelA enzyme-linked immunosorbent assay. Results Treatment with recombinant Hsp70 to wild-type mice in CIP resulted in significant aggravation of inflammation in pancreas, elevated levels of serum cytokines, up-regulation of pulmonary MPO activity and increase of lung tissues TNF-α concentrations. In contrast, treatment with Hsp70 to TLR4-deficient mice had little effect on serum cytokines levels pancreatic inflammation, pulmonary MPO activity and TNF-α concentrations. Conclusions The results suggest that extracellular Hsp70 might induce systemic inflammatory response syndrome （SlRS）-Iike response in vivo and TLR4 might be involved in the Hsp70-mediated activation of inflammatory reaction in the progression of CIP without infection.

关 键 词：acute pancreatitis toll-like receptors PATHOGENESIS heat shock proteins systemic inflammatory response syndrome 

分 类 号：R576[医药卫生—消化系统]