皮质酮诱导小鼠腹腔巨噬细胞发生内质网应激的作用  

Effect of Corticosterone on the Induction of Endoplasmic Reticulum Stress in Mice Peritoneal Macrophages1

作　　者：钟河江[1] 蒋建新[1] 王海燕[1] 杨策[1] 张冲[1] 严军[1] 刘庆[1] 黄苏娜[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所第四研究室,全军交通医学研究所,全军交通伤重点实验室,创伤,烧伤与复合伤国家重点实验室,重庆400042

出　　处：《现代生物医学进展》2009年第7期1233-1236,共4页Progress in Modern Biomedicine

基　　金：国家重点基础研究发展规划项目"(973"项目)(2005CB522602);全军医学科研"十一五"科技攻关项目(06G080)

摘　　要：目的:观察内源性糖皮质激素皮质酮对小鼠腹腔巨噬细胞内质网应激相关蛋白GRP78、XBP1-S及ATF6蛋白表达水平的影响,并探讨皮质酮诱导小鼠腹腔巨噬细胞内质网应激的作用。方法:分离成年雄性C57/BL6小鼠腹腔巨噬细胞,随机分为四组,分别以终浓度为0、10、50及1000ng/ml皮质酮处理小鼠腹腔巨噬细胞,时间为1h,提取细胞总蛋白,应用Westernblotting方法检测内质网分子伴侣GRP78蛋白及未折叠蛋白反应信号转导通路转录因子XBP1-S和ATF6蛋白质表达变化。结果:低浓度皮质酮(10、50ng/ml)处理小鼠腹腔巨噬细胞1h后,均可显著地增加内质网分子伴侣GRP78蛋白表达,以50ng/ml皮质酮组增加最明显,而当皮质酮浓度达1000ng/ml时,GRP78蛋白增加不显著。并且,低浓度皮质酮(10、50ng/ml)可显著增强未折叠蛋白反应两个重要转录因子XBP1-S和p50ATF6蛋白表达。结论:这些结果表明低浓度内源性糖皮质激素皮质酮可诱发小鼠腹腔巨噬细胞发生内质网应激,激活未折叠蛋白质反应信号转导通路,其可能与巨噬细胞免疫功能增强有关。Objective： To observe the expression changes of endoplasmic reticulum （ER） stress-associated proteins GRP78, XBP1-S and ATF6 in mice peritoneal macrophages treated with endogenous glucocorticoids （corticosterone）, and to investigate the effect of corticosterone on the induction of ER stress in mice peritoneal macrophages. Methods： Isolated peritoneal macrophages from adult male C57BL/6 mice were randomly assigned to four groups and treated with corticosterone （0, 10, 50 and 1000 ng/ml） for 1 hour, respectively. Western blotting was used to detect the expression of GRP78, XBP1-S and ATF6 protein in mice peritoneal macrophages.Results：The ER chaperone GRP78 protein expression in mice peritoneal macrophages was significantly induced after stimulation with low concentraction corticosterone （10 and 50 ng/ml） for 1 hour. Maximum expression of GRP78 protein occurred after exposure to 50 ng/ml corticosterone for 1 hour. When stimulated by 1000 ng/ml corticosterone, the expression of GRP78 protein was not markedly increased. Furthermore, The transcription factor XBP1-S and p50 ATF6, two key components of the unfolded protein response （UPR）, were increased after treatment with low concentraction corticosterone （10 and 50 ng/ml）. Conclusion：These findings suggest that low concentraction endogenous glucocorticoids induces ER stress in mouse peritoneal macrophages, activates the UPR signaling pathway, which may contribute to enhancement of mouse pertioneal macrophages immune function.

关 键 词：皮质酮 巨噬细胞 内质网应激 

分 类 号：Q691.5[生物学—生物物理学] Q78