Signaling through JAK2-STAT5 pathway is essential for IL-3-Induced activation of microglia
Signaling through JAK2-STAT5 pathway is essential for IL-3-Induced activation of microglia
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DOI：
10.1002/glia.10316
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发表时间：
2004-01-15
期刊：
影响因子：
6.2
通讯作者：
Muthian, G
中科院分区：
文献类型：
--
作者：
Bright, JJ;Natarajan, C;Muthian, G
小胶质细胞是大脑中的巨噬细胞，介导中枢神经系统（CNS）的免疫和炎症反应。小胶质细胞的活化和炎性细胞因子的分泌与CNS疾病的发病机制相关，包括多发性硬化（MS）、阿尔茨海默病（AD）、帕金森病、朊病毒病和AIDS痴呆。微生物病原体、细胞因子、趋化因子和共刺激分子是CNS中小胶质细胞活化的有效诱导剂。通过其受体的信号传导，IL-3诱导小胶质细胞中JAK-STAT和MAP激酶途径的活化。在这项研究中，我们发现在体外用tyrphostin AG 490处理EOC-20小胶质细胞可以阻断IL-3诱导的JAK 2、STAT 5A和STAT 5 B信号蛋白的酪氨酸磷酸化。用显性负性JAK 2突变体稳定转染EOC-20细胞也阻断了IL-3诱导的小胶质细胞中JAK 2、STAT 5A和STAT 5 B的酪氨酸磷酸化。阻断JAK 2-STAT 5通路可降低IL-3诱导的小胶质细胞增殖和CD 40及主要组织相容性复合物II类分子的表达。这些发现强调了JAK 2-STAT 5信号通路在介导IL-3诱导的小胶质细胞活化中起关键作用的事实。(C)2003 Wiley-Liss，Inc.
Microglia, the resident macrophage of the brain, mediates immune and inflammatory responses in the central nervous system (CNS). Activation of microglia and secretion of inflammatory cytokines associate with the pathogenesis of CNS diseases, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease, prion disease, and AIDS dementia. Microbial pathogens, cytokines, chemokines, and costimulatory molecules are potent inducers of microglial activation in the CNS. Signaling through its receptor, IL-3 induces the activation of JAK-STAT and MAP kinase pathways in microglial cells. In this study, we found that in vitro treatment of EOC-20 microglial cells with tyrphostin AG490 blocked IL-3-induced tyrosine phosphorylation of JAK2, STAT5A, and STAT5B signaling proteins. Stable transfection of EOC-20 cells with a dominant negative JAK2 mutant also blocked IL-3-induced tyrosine phosphorylation of JAK2, STAT5A, and STAT5B in microglia. The blockade of JAK2-STAT5 pathway resulted in a decrease in IL-3-induced proliferation and expression of CD40 and major histocompatibility complex class II molecules in microglia. These findings highlight the fact that JAK2-STAT5 signaling pathway plays a critical role in mediating IL-3-induced activation of microglia. (C) 2003 Wiley-Liss, Inc.