首页|期刊导航|中华医学杂志（英文版）|Extracellular heat-shock protein 70 aggravates cerulein-induced pancreatitis through toll-like receptor-4 in mice
中华医学杂志（英文版）2008，Vol.121Issue(15)：1420-1425,6.
Extracellular heat-shock protein 70 aggravates cerulein-induced pancreatitis through toll-like receptor-4 in mice
Extracellular heat-shock protein 70 aggravates cerulein-induced pancreatitis through toll-like receptor-4 in mice
摘要
Abstract
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-a) concentrations and myeloperoxidase (MPO) activity in both pancreas and lungs were analyzed. The nuclear factor kappa B (NF-KB) 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-a concentrations.Conclusions The results suggest that extracellular HspTO might induce systemic inflammatory response syndrome (SIRS)-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 syndromeKey words
acute pancreatitis/toll-like receptors/pathogenesis/heat shock proteins/systemic inflammatory response syndrome分类
医药卫生引用本文复制引用
SONG Jun-min,WANG Rong,LIU Hong-xiang,LI Yuan,ZENG Yu-jian,ZHOU Zong-guang,LIU Hai-yi,XU Bing,WANG Ling,ZHOU Bin..Extracellular heat-shock protein 70 aggravates cerulein-induced pancreatitis through toll-like receptor-4 in mice[J].中华医学杂志（英文版）,2008,121(15):1420-1425,6.基金项目
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). （No. 30400434 and No. 30571811）
