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
黄承芳;黎钢;孙圣刚;
摘要(Abstract):
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。
关键词(KeyWords): 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
基金项目(Foundation): 国家自然科学基金资助项目(30500574)
作者(Author): 黄承芳;黎钢;孙圣刚;
Email:
DOI:
参考文献(References):
- [1]Carreno-Mller E,Herrera AJ,de Pablos RM,et al.Thrombin induces in vivo degeneration of nigral dopaminergic neurons along with the activation of mi-croglia[J].J Neurochem,2003,84(5):1201-1214.
- [2]Choi SH,Joe EH,Ki mSU,et al.Thrombin-induced microglial activation produces degeneration of nigral dopaminergic neurons in vivo[J].J Neurosci,2003,23(13):5877-5886.
- [3]Choi SH,Lee DY,Ryu JK,et al.Thrombin inducesnigral dopaminergic neurodegenerationin vivo by alte-ring expression of death-related proteins[J].Neurobiol Dis,2003,14(2):181-193.
- [4]Herrera AJ,Toms-Camardiel M,Venero J L,et al.Inflammatory process as a determinant factor for the degeneration of substantia nigra dopaminergic neurons[J].J Neural Transm,2005,112(1):111-119.
- [5]Fuji moto S,Katsuki H,Ohnishi M,et al.Thrombin induces striatal neurotoxicity depending on mitogen-activated protein kinase pathways in vivo[J].Neuro-science,2007,144(2):694-701.
- [6]O’Shea JJ,Pesu M,Borie DC,et al.Anew modality for i mmunosuppression:targeting the JAK/STAT pathway[J].Nat Rev Drug Discov,2004,3(7):555-564.