ER stress活化促进星形胶质细胞NLRP3表达和IL-1β合成分泌  

ER stress activation promotes NLRP3 expression and IL-1β synthesis in Aβ induced astrocytes

作　　者：洪洋 刘彬 夏龙飞 贾佳 刘运江 HONG Yang;LIU Bin;XIA Long-Fei;JIA Jia;LIU Yun-Jiang(The Fourth Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第四医院

出　　处：《中国免疫学杂志》2020年第4期411-414,共4页Chinese Journal of Immunology

摘　　要：目的:研究Aβ所诱星形胶质细胞NLRP3炎症小体和IL-1β合成分泌的可能调节作用及潜在的分子机制。方法:全营养正常培养新生鼠皮层星形胶质细胞,分别应用ELISA、免疫荧光、Western blot等试验方法检测Aβ对于星形胶质细胞ER stress相关GRP78表达的影响,并通过药理学方法研究ER stress激活对于星形胶质细胞NLRP3蛋白表达以及IL-1β合成分泌的影响。结果:相比对照组,Aβ明显促进ER stress相关蛋白GRP78表达。应用ER stress诱导剂TM处理发现,TM显著促进星形胶质细胞IL-1β、pro-IL-1β以及NLRP3合成表达。另外,应用ER stress阻断剂Sal干预后发现,Sal能明显阻断Aβ所致星形胶质细胞NLRP3炎症小体表达活化。结论:Aβ能够诱导星形胶质细胞ER stress活化,并能通过活化ER stress水平显著促进IL-1β、pro-IL-1β和NLRP3炎症小体表达活化。Objective:To investigate the possible regulatory effect and potential molecular mechanism of the IL-1β processing and NLRP3 inflammasome expression in Aβ-induced astrocytes.Methods:Astrocytes of cerebral cortex of newborn SD rat pups were enrich-cultured,and detected GRP78 expression in Aβ treated astrocytes by immunofluorescence.In addition,the level of IL-1β in the supernatant and NLRP3 expression in the lysates of astrocytes were detected following ER stress inducer TM or Aβ treatment by ELISA,Western blot.Pharmacological methods blocked the activation of ER stress,and then studied the effect of ER stress activation on NLRP3 expression and IL-1β processing.Results:Compared with the control group,Aβ significantly promoted ER stress related protein GRP78 expression.Treated with ER stress inducer TM,the synthesis and secretion of IL-1β and NLRP3 expression was significantly increased in astrocytes.In addition,following ER stress blocker Sal treatment,it was found that Sal significantly inhibited the activation of NLRP3 inflammasome in astrocytes.Conclusion:Aβ can induce ER stress activation in astrocytes and significantly promote IL-1β processing and NLRP3 inflammasome expression by activating ER stress.

关 键 词：ER STRESS NLRP3 AΒ 星形胶质细胞 

分 类 号：R741.02[医药卫生—神经病学与精神病学]