Neuronal Injury Induces Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) Production in Astrocytes
Neuronal Injury Induces Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) Production in Astrocytes
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DOI：
10.1254/jphs.08298fp
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发表时间：
2009-01-01
影响因子：
3.5
通讯作者：
Minami, Masabumi
中科院分区：
文献类型：
--
作者：
Katayama, Takahiro;Tanaka, Hiroki;Minami, Masabumi
越来越多的证据表明，神经炎症在缺血性和兴奋性中毒性脑损伤中起着关键作用。细胞因子诱导的中性粒细胞趋化因子-1(CINC-1)是一种CXC趋化因子，参与炎症细胞向脑实质的渗透。在本研究中，我们研究了N-甲基-D-天冬氨酸(NMDA)诱导的神经元损伤对器官型皮质-纹状体脑片培养中CINC-1产生的影响。50mU的N-甲基-D-天冬氨酸处理3-4h，对神经元造成毁灭性的损伤，并增加CINC-1的产生。免疫组织化学分析表明，CINC-1免疫反应主要见于星形胶质细胞。NMDA不能诱导富集型星形胶质细胞培养和去神经元培养的星形胶质细胞产生CINC-I，提示NMDA作用于神经细胞诱导星形胶质细胞产生CINC-1。丝裂原活化蛋白激酶/细胞外信号调节激酶(ERK)抑制剂U0126可显著抑制NMDA诱导的CINC-1mRNA表达。这些结果表明，NMDA诱导的神经元损伤通过MEK/ERK信号通路诱导星形胶质细胞CINC-1的产生。对这一信号通路的操纵可能成为抑制神经炎症从而治疗缺血性脑损伤的靶点。
Accumulating evidence indicates a pivotal role for neuroinflammation in ischemic and excitotoxic brain injury. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) is a CXC chemokine implicated in the infiltration of inflammatory cells into the brain parenchyma. In this study, we investigated the effect of N-methyl-D-aspartate (NMDA)-induced neuronal injury on CINC-1 production in the organotypic cortico-striatal slice cultures. Treatment with 50 mu M NMDA for 3-4h caused devastating neuronal damage and increased CINC-1 production. Immunohistochemical analysis revealed that the CINC-1 immunoreactivity was predominantly detected in astrocytes. NMDA failed to induce CINC-I production in enriched astrocyte cultures or neuron-depleted slice cultures, suggesting that NMDA acted on neuronal cells to induce astrocytic CINC-1 production. NMDA-induced CINC-1 mRNA expression was significantly inhibited by U0126, a mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor. These results suggest that NMDA-evoked neuronal injury induced astrocytic CINC-1 production via a MEK/ERK signaling pathway. Manipulation of this signaling pathway may serve as a target for suppressing neuroinflammation and, thereby, treating ischemic brain injury.