TGF-beta suppresses IFN-gamma induction of class II MHC gene expression by inhibiting class II transactivator messenger RNA expression
| Autor: | Y J Lee, Y Han, H T Lu, V Nguyen, H Qin, P H Howe, B A Hocevar, J M Boss, R M Ransohoff, E N Benveniste |
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| Rok vydání: | 1997 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 158:2065-2075 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.158.5.2065 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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