|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
9
|
|
pubmed:dateCreated |
2000-11-3
|
|
pubmed:abstractText |
We and others have reported that IFN-alpha potentiates the apoptotic effects of TNF through a mechanism that is not understood. Because the nuclear transcription factors NF-kappaB and AP-1 have recently been reported to mediate anti-apoptosis and cell survival, we hypothesized that IFN-alpha potentiates the cytotoxic effects of TNF by suppressing TNF-induced activation of NF-kappaB and AP-1. We tested this hypothesis by pretreating human Jurkat T cells with IFN-alpha, which blocked TNF-induced activation of NF-kappaB and AP-1 in a time- and dose-dependent manner as determined by EMSA. IFN-alpha blocked TNF-induced phosphorylation and degradation of the inhibitor subunit of NF-kappaB, and suppressed NF-kappaB and AP-1 activation induced by various other inflammatory stimuli. NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TNF receptor-associated factor 2, and NF-kappaB-inducing kinase was also abrogated by IFN-alpha pretreatment. The suppression of NF-kappaB and AP-1 correlated with the potentiation of TNF-induced cytotoxicity and caspase activation. Overall our results suggest that IFN-alpha potentiates the apoptotic effects of TNF possibly by suppressing NF-kappaB and AP-1 activation.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/I-kappa B Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Immunosuppressive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B p50 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappaB inhibitor alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor RelA,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Nov
|
|
pubmed:issn |
0022-1767
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
165
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
4927-34
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:11046018-Apoptosis,
pubmed-meshheading:11046018-Caspases,
pubmed-meshheading:11046018-Ceramides,
pubmed-meshheading:11046018-Cytotoxicity, Immunologic,
pubmed-meshheading:11046018-DNA-Binding Proteins,
pubmed-meshheading:11046018-Drug Synergism,
pubmed-meshheading:11046018-Enzyme Activation,
pubmed-meshheading:11046018-Gene Expression Regulation,
pubmed-meshheading:11046018-Genes, Reporter,
pubmed-meshheading:11046018-Humans,
pubmed-meshheading:11046018-I-kappa B Proteins,
pubmed-meshheading:11046018-Immunosuppressive Agents,
pubmed-meshheading:11046018-Interferon-alpha,
pubmed-meshheading:11046018-Jurkat Cells,
pubmed-meshheading:11046018-Lipopolysaccharides,
pubmed-meshheading:11046018-NF-kappa B,
pubmed-meshheading:11046018-NF-kappa B p50 Subunit,
pubmed-meshheading:11046018-Phosphorylation,
pubmed-meshheading:11046018-Transcription Factor AP-1,
pubmed-meshheading:11046018-Transcription Factor RelA,
pubmed-meshheading:11046018-Transfection,
pubmed-meshheading:11046018-Tumor Necrosis Factor-alpha
|
|
pubmed:year |
2000
|
|
pubmed:articleTitle |
IFN-alpha suppresses activation of nuclear transcription factors NF-kappa B and activator protein 1 and potentiates TNF-induced apoptosis.
|
|
pubmed:affiliation |
Cytokine Research Laboratory, Department of Bioimmunotherapy, MD Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
