Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-3-21
pubmed:abstractText
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 results in decreased IFN-gamma promoter activity and reduced IFN-gamma production.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
168
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3520-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11907114-Consensus Sequence, pubmed-meshheading:11907114-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:11907114-Down-Regulation, pubmed-meshheading:11907114-Gene Expression Regulation, Bacterial, pubmed-meshheading:11907114-Humans, pubmed-meshheading:11907114-Interferon-gamma, pubmed-meshheading:11907114-Intracellular Fluid, pubmed-meshheading:11907114-Jurkat Cells, pubmed-meshheading:11907114-Mycobacterium tuberculosis, pubmed-meshheading:11907114-NF-kappa B, pubmed-meshheading:11907114-Nuclear Proteins, pubmed-meshheading:11907114-Promoter Regions, Genetic, pubmed-meshheading:11907114-Protein Binding, pubmed-meshheading:11907114-RNA, Messenger, pubmed-meshheading:11907114-T-Lymphocytes, pubmed-meshheading:11907114-Transfection, pubmed-meshheading:11907114-Tuberculin, pubmed-meshheading:11907114-Tuberculosis
pubmed:year
2002
pubmed:articleTitle
Reduced expression of nuclear cyclic adenosine 5'-monophosphate response element-binding proteins and IFN-gamma promoter function in disease due to an intracellular pathogen.
pubmed:affiliation
Department of Microbiology and Immunology, and Center for Pulmonary and Infectious Disease Control, University of Texas Health Center, Tyler, TX 75708, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't