JAK2-STAT3途径介导凝血酶诱导的小胶质细胞TNF-α的激活  

JAK2-STAT3 Signaling Pathway Mediates Thrombin-induced TNF-α Action of Microglia in vitro

作　　者：黄承芳[1] 黎钢[1] 孙圣刚[1] 

机构地区：[1]华中科技大学附属协和医院神经内科,湖北武汉430022

出　　处：《中国神经免疫学和神经病学杂志》2008年第4期270-273,共4页Chinese Journal of Neuroimmunology and Neurology

基　　金：国家自然科学基金资助项目(30500574)

摘　　要：目的 探讨Janus激酶2/信号转导和转录激活子3（JAK2/STAT3）途径可否介导凝血酶诱导的小胶质细胞肿瘤坏死因子（TNF-α）激活。方法 采用20U/mL凝血酶或AG490预处理（10μmol/L）＋凝血酶（20U/mL）处理原代培养的小胶质细胞,经Western Blot法检测细胞Janus激酶1（JAK1）、磷酸化（P）-JAK1、P-JAK2、磷酸化-信号转导和转录激活子3（P-STAT3）、STAT3表达,酶联免疫吸附（ELISA）法检测血清上清液TNF-α水平。结果 经凝血酶处理2-12h后JAK2、STAT3发生了磷酸化,3-48h后TNF-α表达增加。经JAK激酶抑制剂AG490预处理后再经凝血酶处理的小胶质细胞的JAK2和STAT3激活显著减少,且TNF-α释放被抑制。结论 JAK2-STAT3途径可介导凝血酶诱导的小胶质细胞TNF-α激活。Objective The present study explored whether janus kinase 2/signal transducer and activator of transcription 3（JAK2/STAT3） signaling pathway mediates thrombin-induced tumor necrosis factor α（TNF-α） action of microglia in vitro. Methods After 20 U/mL thrombin or AG490（10 μmol/L）＋thrombin-treated primary rat microglial cells at indicated time, Western Blot analysis were performed to examine production of JAK2, P-JAK1, P-JAK2, P-STAT3, STAT3. ELISA evaluated the levels of TNF-α in the supernatant obtained from thrombin-activated ventral mesencephalons microglia. Results After thrombin-treated primary rat microglial cells, thrombin activated JAK2 and induced phosphorylation of STAT3 within 2～12 h. In addition to, thrombin increased production of the inflammation-associated TNF-α at 3 h. However,AG490, a JAK inhibitor, markedly reduced activation of JAK2 and STAT3 in thrombin treated-microglia, also inhibited thrombin-induced release of TNF-α. Conclusions These results suggested that JAK2-STAT3 signaling pathway mediated thrombin-induced TNF-α action of microglia in vitro.

关 键 词：凝血酶 小胶质细胞 Janus激酶2/信号转导和转录激活子3途径 肿瘤坏死因子 

分 类 号：R734.1[医药卫生—肿瘤]