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首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Kinase inhibitors abrogate IFN-gamma-induced class II transactivator and class II MHC gene expression in astroglioma cell lines.
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Kinase inhibitors abrogate IFN-gamma-induced class II transactivator and class II MHC gene expression in astroglioma cell lines.

机译：激酶抑制剂消除了星形胶质瘤细胞系中IFN-γ诱导的II类反式激活因子和II类MHC基因的表达。

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摘要

Multiple kinase events, involving both tyrosine (tyr) kinase and serine/threonine (ser/thr) kinase activity, are required for IFN-gamma-induced class II MHC mRNA and protein expression in primary rat astrocytes. In this study, we examined the necessity of ser/thr and tyr kinase activity for IFN-gamma-induced stimulation of class II MHC gene expression in the human astroglioma cell lines CRT and CH235, as well as the involvement of these kinases in IFN-gamma-induced expression of the class II transactivator (CIITA), a protein critical for IFN-gamma-induced transcription of class II MHC genes. We show that general ser/thr kinase inhibitors, inhibitors of the ser/thr kinase mitogen-activated protein kinase (MAPK), and tyr kinase inhibitors reduce IFN-gamma-induced class II MHC mRNA and protein expression in a dose-dependent manner. As well, these inhibitors abrogate IFN-gamma-induced CIITA mRNA expression in the astroglioma cell lines. We have further demonstrated that cells constitutively expressing the CIITA protein (2fTGH.CIITA) show no decrease in CIITA or class II MHC mRNA expression in the presence of ser/thr and tyr kinase inhibitors. Collectively, these data indicate that ser/thr kinase activity, possibly MAPK, and tyr kinase activity are required for IFN-gamma-induced expression of CIITA mRNA, and the subsequent expression of class II MHC genes.
机译：IFN-γ诱导的II类MHC mRNA和蛋白在原代大鼠星形胶质细胞中的表达需要涉及酪氨酸（tyr）激酶和丝氨酸/苏氨酸（ser / thr）激酶活性的多种激酶事件。在这项研究中，我们研究了ser / thr和tyr激酶活性对于人星形胶质瘤细胞系CRT和CH235中IFN-γ诱导的II类MHC基因表达刺激的必要性，以及这些激酶与IFN-γ的关系。 γ诱导的II类反式激活因子（CIITA）的表达，该蛋白对于IFN-γ诱导的II类MHC基因转录至关重要。我们显示，一般的ser / thr激酶抑制剂，ser / thr激酶促分裂原活化蛋白激酶（MAPK）和tyr激酶抑制剂均以剂量依赖性方式降低IFN-γ诱导的II类MHC mRNA和蛋白表达。同样，这些抑制剂消除了星形胶质瘤细胞系中IFN-γ诱导的CIITA mRNA表达。我们进一步证明，在存在ser / thr和tyr激酶抑制剂的情况下，组成型表达CIITA蛋白（2fTGH.CIITA）的细胞在CIITA或II类MHC mRNA表达上没有降低。总的来说，这些数据表明，IFN-γ诱导的CIITA mRNA表达和随后的II类MHC基因表达需要ser / thr激酶活性，可能是MAPK和tyr激酶活性。

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