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- W4313335871 endingPage "1440" @default.
- W4313335871 startingPage "1435" @default.
- W4313335871 abstract "Abstract Precise regulation of MHC class II gene expression is crucial for development and function of the immune system. Class II trans-activator (CIITA) has been shown to be required for constitutive and IFN-γ-induced MHC class II transcription. TNF-α is commonly coexpressed with IFN-γ during immune-mediated inflammatory responses and modulates IFN-γ-stimulated MHC class II expression. The effect of TNF-α on MHC class II expression depends on cell type and cellular differentiation state. We show here that TNF-α suppresses IFN-γ-induced CIITA mRNA accumulation, resulting in decreased MHC class II expression in human fibrosarcoma HT1080 cells. TNF-α also inhibits CIITA mRNA accumulation and protein expression in a tetracycline-regulated system without affecting promoter activity. CIITA mRNA, regulated by either IFN-γ or tetracycline, was destabilized in the presence of TNF-α, suggesting that TNF-α utilizes a distinct mechanism to suppress MHC class II expression in HT1080 cells. Consistent with this interpretation, TNF-α blocked IFN-γ-induced CIITA and MHC class II expression in mutant cells that are unresponsive to TGF-β or IFN-β. This is the first instance in which MHC class II expression is inhibited by destabilizing CIITA mRNA." @default.
- W4313335871 created "2023-01-06" @default.
- W4313335871 creator A5005706548 @default.
- W4313335871 creator A5020908862 @default.
- W4313335871 creator A5034732141 @default.
- W4313335871 date "1999-08-01" @default.
- W4313335871 modified "2023-10-14" @default.
- W4313335871 title "TNF-α Suppresses IFN-γ-Induced MHC Class II Expression in HT1080 Cells by Destabilizing Class II<i>trans</i>-Activator mRNA" @default.
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- W4313335871 doi "https://doi.org/10.4049/jimmunol.163.3.1435" @default.
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