Upregulation of RANTES gene expression in neuroglia by Japanese encephalitis virus infection
Upregulation of RANTES gene expression in neuroglia by Japanese encephalitis virus infection
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DOI：
10.1128/jvi.78.22.12107-12119.2004
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发表时间：
2004-11-01
影响因子：
5.4
通讯作者：
Raung, SL
中科院分区：
文献类型：
--
作者：
Chen, CJ;Chen, JH;Raung, SL
日本脑炎病毒（JEV）感染引起脑炎症并刺激炎性细胞因子表达。神经胶质细胞协调免疫细胞募集到中枢神经系统（CNS）内的病毒感染的焦点部位，并通过细胞因子和趋化因子的调节网络使免疫细胞功能同步。由于免疫细胞浸润是突出的，我们研究了响应的化学引诱物，RANTES（调节激活，正常T细胞表达和分泌）的生产，在响应JEV感染的神经胶质细胞：感染JEV被发现引发生产的RANTES从初级神经元/神经胶质细胞，混合神经胶质细胞，小胶质细胞，和星形胶质细胞，但不是从神经元培养。RANTES的产生似乎并不直接导致JEV诱导的神经元死亡，而是有助于免疫细胞的募集。RANTES表达需要病毒复制和细胞外信号调节激酶（ERK）以及转录因子（包括核因子κ B（NF-κ B）和核因子IL-6（NF-IL-6））的激活。JEV感染诱导胶质细胞表达RANTES需要NF-κ B和NF-IL-6的协同激活。使用酶抑制剂，我们证明了ERK信号通路和RANTES表达之间的强相关性。然而，JEV复制不依赖于ERK、NF-kappaB和NF-IL-6的激活。总之，这些结果表明，由JEV感染的胶质细胞提供了早期ERK-，NF-κ B-和NF-IL-6介导的信号，直接激活RANTES表达，这可能涉及在中枢神经系统的炎症反应的启动和放大。
Infection with Japanese encephalitis virus (JEV) causes cerebral inflammation and stimulates inflammatory cytokine expression. Glial cells orchestrate immunocyte recruitment to focal sites of viral infection within the central nervous system (CNS) and synchronize immune cell functions through a regulated network of cytokines and chemokines. Since immune cell infiltration is prominent, we investigated the production of a responding chemoattractant, RANTES (regulated upon activation, normal T-cell expressed and secreted), in response to JEV infection of glial cells: Infection with JEV was found to elicit the production of RANTES from primary neurons/glia, mixed glia, microglia, and astrocytes but not from neuron cultures. The production of RANTES did not seem to be directly responsible for JEV-induced neuronal death but instead contributed to the recruitment of immune cells. RANTES expression required viral replication and the activation of extracellular signal-regulated kinase (ERK) as well as transcription factors, including nuclear factor kappa B (NF-kappaB) and nuclear factor IL-6 (NF-IL-6). The induction of RANTES expression by JEV infection in glial cells needed the coordinate activation of NF-kappaB and NF-IL-6. Using enzymatic inhibitors, we demonstrated a strong correlation between the ERK signaling pathway and RANTES expression. However, JEV replication was not dependent on the activation of ERK, NF-kappaB, and NF-IL-6. Altogether, these results demonstrated that infection of glial cells by JEV provided the early ERK-, NF-kappaB-, and NF-IL-6-mediated signals that directly activated RANTES expression, which might be involved in the initiation and amplification of inflammatory responses in the CNS.