Reduced expression of nuclear cyclic adenosine 5'-monophosphate response element-binding proteins and IFN-gamma promoter function in disease due to an intracellular pathogen

The Journal of Immunology : Official Journal of the American Association of Immunologists
B SamtenP F Barnes

Abstract

Mycobacterium tuberculosis-induced IFN-gamma protein and mRNA expression have been shown to be reduced in tuberculosis patients, compared with healthy tuberculin reactors. To determine whether this decrease was associated with reduced activity of the IFN-gamma promoter, we first studied binding of nuclear proteins to the radiolabeled proximal IFN-gamma promoter (-71 to -40 bp), using EMSAs with nuclear extracts of freshly isolated peripheral blood T cells. Nuclear extracts of T cells from most tuberculosis patients showed markedly reduced expression of proteins that bind to the proximal IFN-gamma promoter, compared with findings in nuclear extracts of T cells from healthy tuberculin reactors. These DNA-binding complexes contained CREB proteins, based on competitive EMSAs, supershift assays, and Western blotting with an anti-CREB Ab. Transient transfection of PBLs with a luciferase reporter construct under the control of the IFN-gamma promoter revealed reduced IFN-gamma promoter activity in tuberculosis patients. Transient transfection of Jurkat cells with a dominant-negative CREB repressor plasmid reduced IFN-gamma promoter activity. These data suggest that reduced expression of CREB nuclear proteins in tuberculosis patients re...Continue Reading

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Citations

Mar 7, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xisheng WangBuka Samten
Nov 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Angela ColmoneChyung-Ru Wang
Aug 21, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xisheng WangBuka Samten
Mar 11, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Buka SamtenPeter F Barnes
May 10, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Buka SamtenPeter F Barnes
Jul 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Buka SamtenPeter F Barnes
Sep 14, 2017·Journal of Molecular Microbiology and Biotechnology·Federico Carlos BlancoFabiana Bigi
Jun 25, 2003·Current Opinion in Infectious Diseases·Eun-Kyeong JoHazel M Dockrell
Aug 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shingo YanoDan L Longo

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