Activation of astrocyte intracellular signaling pathways by interleukin-1 in rat primary striatal cultures
Activation of astrocyte intracellular signaling pathways by interleukin-1 in rat primary striatal cultures
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DOI：
10.1002/glia.10010
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发表时间：
2002-01-01
期刊：
影响因子：
6.2
通讯作者：
McNulty, S
中科院分区：
文献类型：
--
作者：
Dunn, SL;Young, EA;McNulty, S
纹状体。已被认为是介导白细胞介素1(IL-1)在缺血时的神经毒性作用的作用部位。然而，这些事件背后的分子机制尚未完全解决。本研究以原代培养的大鼠纹状体细胞为模型，研究纹状体中IL-1信号转导途径。免疫细胞化学分析表明，这些培养物由神经元和星形胶质细胞组成，并在两种类型的细胞上均表达IL-1I型受体(IL-1RI)。IL-1(3U/ml)作用10min可增加纹状体细胞p38MAPK的磷酸化水平。内源性IL-1RI抑制剂IL-1ra(24 ng/ml)和p38 MAP激酶抑制剂SB203580(10 NM)均抑制这一反应。分析IL-1对转录因子核因子-kB核转位的影响，发现核因子-kB以时间依赖的方式被激活。免疫细胞化学显示IL-1仅刺激星形胶质细胞p38的磷酸化和核因子-kB的易位。TaqMan实时定量聚合酶链式反应分析显示，IL-1刺激纹状体培养细胞肿瘤坏死因子-α的基因表达。P38MAPK抑制剂SB203580不能抑制IL-1对核因子-kB转位或基因转录的影响。这些研究已经证明了在培养的纹状体中IL-1信号级联的重要方面。特别令人感兴趣的是，IL-1仅能刺激纹状体星形胶质细胞中p38蛋白激酶和核因子-kB的激活。Glia 37：31-42,2002。(C)2002年Wiley-Liss，Inc.
The striatum. has been implicated as the site of action mediating neurotoxic effects of interleukin-1 (IL-1) during ischemia. However, the molecular mechanisms underlying these events have yet to be fully addressed. In the present study, primary cultures of rat striatal cells were used as a model for the study of IL-1 signaling pathways in the striatum. Immunocytochemical analyses revealed that these cultures consisted of a mixture of neurones and astrocytes and demonstrated expression of the IL-1 type I receptor (IL-1RI) on both cell types. Treatment with IL-1 (3 units/ml) for 10 min increased phosphorylation of p38 MAP kinase in striatal cells. The endogenous IL-1RI inhibitor IL-1Ra (24 ng/ml) and the p38 MAP kinase inhibitor SB203580 (10 nM) both inhibited this response. Analysis of the effects of IL-1 on nuclear translocation of the transcription factor NF-kB revealed that NF-kB became activated in a time-dependent manner. Immunocytochemistry revealed that IL-1 stimulated p38 phosphorylation and NF-kB translocation in astrocytes only. TaqMan real-time quantitative PCR analysis revealed that IL-1 stimulated gene expression of tumor necrosis factor-alpha (TNF) in striatal cultures. The p38 MAP kinase inhibitor SB203580 failed to inhibit the effects of IL-1 on NF-kB translocation or gene transcription. These studies have demonstrated significant aspects of the IL-1 signaling cascade in cultured striatum. Of particular interest is the finding that IL-1 stimulated activation of p38 MAP kinase and NF-kB in striatal astrocytes exclusively. GLIA 37:31-42, 2002. (C) 2002 Wiley-Liss, Inc.