Stat1 alpha expression is involved in IFN-gamma induction of the class II transactivator and class II MHC genes.
Stat1 alpha expression is involved in IFN-gamma induction of the class II transactivator and class II MHC genes.
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DOI：
10.4049/jimmunol.157.4.1559
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发表时间：
1996-08
影响因子：
4.4
通讯作者：
Yi-Ju Lee;E. Benveniste
中科院分区：
文献类型：
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作者：
Yi-Ju Lee;E. Benveniste
II类MHC Ags通过将Ag呈递到T淋巴细胞，导致其活化和分化，在调节免疫反应中起关键作用。II类表达在正常中枢神经系统中很少见，但在一些神经系统疾病中，胶质细胞上的表达升高。我们之前已经证明，ifn - γ诱导的胶质细胞II类表达涉及酪氨酸激酶和蛋白激酶c的激活。ifn - γ诱导酪氨酸激酶Jak1和Jak2以及Stat1 α的酪氨酸磷酸化。此外，ifn - γ增强Stat1 α mRNA和蛋白的表达。我们利用Stat1 α的反义寡核苷酸直接确定ifn - γ诱导的Stat1 α激活和/或增强是否参与II类表达。短暂转染CH235-MG星形胶质瘤细胞，引入Stat1 α mRNA互补的反义寡核苷酸；这种处理抑制了组成型和ifn - γ增强的Stat1 α表达。暴露于Stat1 α反义寡核苷酸的细胞中，ifn - γ诱导的II类MHC表达也受到抑制。II类启动子不包含ifn - γ激活的结合Stat1 α的序列，这表明Stat1 α必须激活另一个直接参与II类表达的蛋白质。一个可能的候选者是II类MHC转激活剂（CIITA）。用Stat1 α的反义寡核苷酸处理的细胞中，ifn - γ诱导的CIITA mRNA也被抑制。这些发现表明Stat1 α参与ifn - γ诱导CIITA表达，导致II类MHC表达。
Class II MHC Ags are critical in the regulation of immune responses by presenting Ag to T lymphocytes, resulting in their activation and differentiation. Class II expression is rare in the normal central nervous system, but elevated expression on glial cells has been observed in several neurologic diseases. We have previously demonstrated that IFN-gamma-induced class II expression in glial cells involves activation of both tyrosine kinase and protein kinase C. IFN-gamma induces tyrosine phosphorylation of the tyrosine kinases Jak1 and Jak2 and of Stat1 alpha. In addition, IFN-gamma enhances expression of Stat1 alpha mRNA and protein. We utilized antisense oligonucleotides against Stat1 alpha to determine directly whether IFN-gamma-induced activation and/or enhancement of Stat1 alpha is involved in class II expression. Antisense oligonucleotides complementary to Stat1 alpha mRNA were introduced in CH235-MG astroglioma cells by transient transfection; such treatment inhibited both constitutive and IFN-gamma-enhanced expression of Stat1 alpha. IFN-gamma-induced class II MHC expression was also inhibited in cells exposed to Stat1 alpha antisense oligonucleotides. The fact that the class II promoter does not contain IFN-gamma-activated sequences for binding Stat1 alpha suggests that Stat1 alpha must activate another protein that is directly involved in class II expression. A likely candidate is the class II MHC transactivator (CIITA). IFN-gamma induction of CIITA mRNA was also inhibited in cells treated with antisense oligonucleotides against Stat1 alpha. These findings demonstrate that Stat1 alpha is involved in IFN-gamma induction of CIITA expression, resulting in class II MHC expression.