热联合内毒素打击对THP-1细胞HMGB1分泌的诱导作用研究  

Mechanism of HMGB1 secretion from THP-1 cells induced by double insults of heat and LPS

作　　者：童华生[1] 段鹏凯[1] 张兴钦[1] 万鹏[1] 安晓庆[1] 唐丽群[1] 苏磊[1] 

机构地区：[1]广州军区广州总医院重症医学科、全军热区创伤救治与组织修复重点实验室,广州510010

出　　处：《解放军医学杂志》2014年第8期640-644,共5页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(81101406);广东省自然科学基金研究团队项目(S2013030013217)~~

摘　　要：目的探讨热联合内毒素(LPS)双重打击对炎症细胞分泌HMGB1的影响及相关机制。方法建立THP-1细胞热和LPS双重打击模型,采用Western blotting检测胞内和分泌性HMGB1水平变化,p38丝裂原活化蛋白激酶(p38MAPK)磷酸化水平变化,并观察特异性抑制p38 MARK磷酸化对THP-1细胞分泌HMGB1水平的影响。结果热联合LPS打击后,THP-1细胞内HMGB1蛋白水平与正常对照组比较明显下降(P<0.05)。热联合LPS组THP-1细胞分泌HMGB1水平与LPS组比较明显升高(P<0.05)。热联合LPS组p38 MAPK磷酸化活性与LPS组比较进一步增强(P<0.05);采用p38MAPK磷酸化特异性抑制剂SB203580预处理THP-1细胞后,可明显提高热联合LPS刺激后胞内HMGB1水平(P<0.05),同时明显减少HMGB1分泌(P<0.05)。结论热联合LPS刺激可促进炎症细胞HMGB1的分泌,这种分泌作用的增强与p38MAPK信号通路有关。Objective To observe the influences of a double insult of heat stress and endotoxin on secretion of HMGB 1 from a strain of pro-inflammatory ceils. Methods A double insult model of heat and lipopolysaccharide （LPS） was reproduced, then intracellular and secreted HMGB 1 levels and p38 MAPK phosphorylation level of THP-1 cells under the stimulation of heat alone or combined with LPS were determined by Western blotting. After pre-treatment with SB203580, the changes in levels of intracellular and secreted HMGB1 in THP-1 cells were observed. Results Intracellular HMGB1 protein expression significantly decreased after heat stress and LPS stimulation （P〈0.05）. LPS induced more intensively p38 mitogen-activated protein kinase （p38 MAPK） phosphorylation in heat and LPS group compared with that in LPS-treated group. Heat further intensified the phosphorylation activity of LPS （P〈0.05）. After pre-treatment of SB203580, intracellular HMGB1 levels increased significantly （P〈0.05） while the secreted HMGB1 levels were reduced in the heat and LPS group （P〈0.05）. Conclusion Combined heat and LPS stimulation can promote HMGB1 secretion from pro-inflammatory cells, which is possibly related to p38 MAPK phosphorylation.

关 键 词：热休克反应 内毒素类 炎症 

分 类 号：R594.12[医药卫生—内科学]