TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression.
TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression.
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DOI：
10.4049/jimmunol.158.5.2065
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发表时间：
1997-03
影响因子：
4.4
通讯作者：
Yi-Ju Lee;Yulong Han;Hong Tao Lu;V. Nguyen;H. Qin;P. Howe;B. A. Hocevar;J. Boss;R. Ransohoff;E. Benveniste
中科院分区：
文献类型：
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作者：
Yi-Ju Lee;Yulong Han;Hong Tao Lu;V. Nguyen;H. Qin;P. Howe;B. A. Hocevar;J. Boss;R. Ransohoff;E. Benveniste
最近，非DNA结合蛋白，II类反式激活因子（CIITA），已被证明是必需的组成型和IFN-γ诱导的II类MHC转录。细胞因子TGF-β在转录水平抑制IFN-γ诱导的II类MHC表达。在这项研究中，我们提供了TGF-β阻断IFN-γ诱导的CIITA mRNA积累的证据。TGF-β下调人类星形胶质瘤和纤维肉瘤细胞系中II类MHC和CIITA mRNA的积累，但TGF-β不会使CIITA信息不稳定，表明在转录水平上的作用。在稳定过表达CIITA的细胞中，导致组成型II类MHC阳性表型，TGF-β对II类MHC的抑制作用被废除，但细胞仍然对TGF-β诱导基因的表达有反应。具有TGF-β信号传导缺陷的细胞系也变得难以抑制IFN-γ诱导的CIITA和II类MHC表达。我们的数据表明，TGF-β抑制IFN-γ诱导的II类MHC表达抑制CIITA mRNA的积累。
Recently, a non-DNA binding protein, class II transactivator (CIITA), has been shown to be required for constitutive and IFN-gamma-inducible class II MHC transcription. The cytokine TGF-beta inhibits IFN-gamma-induced class II MHC expression at the transcriptional level. In this study, we provide evidence that TGF-beta blocks IFN-gamma-induced CIITA mRNA accumulation. TGF-beta down-regulates class II MHC and CIITA mRNA accumulation in human astroglioma and fibrosarcoma cell lines, but TGF-beta does not destabilize the CIITA message, suggesting an effect at the transcriptional level. In cells that stably overexpressed CIITA, leading to a constitutive class II MHC-positive phenotype, the inhibitory effect of TGF-beta on class II MHC was abrogated, but the cells remained responsive for expression of TGF-beta-inducible genes. Cell lines that possessed defects in TGF-beta signaling also became refractory to inhibition of IFN-gamma-induced CIITA and class II MHC expression. Our data indicate that TGF-beta suppresses IFN-gamma-induced class II MHC expression by inhibiting accumulation of CIITA mRNA.