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- W1982485436 abstract "1α,25-Dihydroxyvitamin D3 [1225-(OH)2D3] exerts several effects on the immune system, by regulating lymphocyte proliferation, differentiation of monocytes and secretion of cytokines as IL-2, granulocyte-macrophage colony-stimulating factor and IFN-γ in T cells. Here, we analyze the effect of 1,25-(OH)2D3 on IFN-γ gene transcription. Transient transfection assays in Jurkat T cells indicate that activation of the IFN-γ promoter is down-regulated by 1,25-(OH)2D3. This effect is enhanced by retinoid X receptor (RXR), and a functional vitamin D3 receptor (VDR) DNA-binding domain in necessary for repression. We delineated two important promoter regions mainly involved in this modulation. The first of these is situated at the level of a promoter-silencer previously characterized and binds the heterodimer VDR-RXR in electrophoretic mobility shift assay. Residual negative regulation was also detected at the level of the promoter fragment – 108 to + 64 bp from the transcription start site and, surprisingly, the activity of the IFN-γ enhancer from – 108 to – 36 bp in the context of a heterologous promoter was not affected by 1,25-(OH)2D3. Moreover, binding activity for VDR-RXR has been detected in the IFN-γ minimal promoter, suggesting a possible mechanism of interference with transcription initiation/progression. The overall data indicate that direct modulation of the IFN-γ promoter activity is one of the possible mechanisms involved in the repressive effect of 1,25-(OH)2D3 on IFN-γ gene expression." @default.
- W1982485436 created "2016-06-24" @default.
- W1982485436 creator A5024871281 @default.
- W1982485436 creator A5062614877 @default.
- W1982485436 date "1998-10-01" @default.
- W1982485436 modified "2023-09-27" @default.
- W1982485436 title "Vitamin D3: a transcriptional modulator of the interferon-γ gene" @default.
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- W1982485436 doi "https://doi.org/10.1002/(sici)1521-4141(199810)28:10<3017::aid-immu3017>3.0.co;2-6" @default.
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