Lee Y J, Han Y, Lu H T, Nguyen V, Qin H, Howe P H, Hocevar B A, Boss J M, Ransohoff R M, Benveniste E N
Department of Cell Biology, University of Alabama at Birmingham, 35294, USA.
J Immunol. 1997 Mar 1;158(5):2065-75.
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.
最近，一种非DNA结合蛋白，即II类反式激活因子（CIITA），已被证明是组成型和IFN-γ诱导的II类MHC转录所必需的。细胞因子TGF-β在转录水平上抑制IFN-γ诱导的II类MHC表达。在本研究中，我们提供证据表明TGF-β阻断IFN-γ诱导的CIITA mRNA积累。TGF-β下调人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，提示其在转录水平上发挥作用。在稳定过表达CIITA从而导致组成型II类MHC阳性表型的细胞中，TGF-β对II类MHC的抑制作用被消除，但这些细胞对TGF-β诱导基因的表达仍有反应。在TGF-β信号传导方面存在缺陷的细胞系也对IFN-γ诱导的CIITA和II类MHC表达的抑制产生抗性。我们的数据表明，TGF-β通过抑制CIITA mRNA的积累来抑制IFN-γ诱导的II类MHC表达。
