Source:http://linkedlifedata.com/resource/pubmed/id/11544310
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
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| pubmed:dateCreated |
2001-9-6
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| pubmed:abstractText |
Aging and chronic inflammatory syndromes, such as rheumatoid arthritis, are associated with high frequencies of CD4(+)CD28(null) T cells, which are rarely seen in healthy individuals younger than 40 years. Inasmuch as rheumatoid arthritis and aging are also associated with elevated levels of TNF-alpha, we examined whether this proinflammatory cytokine influences CD28 expression. Incubation of T cell lines and clones as well as Jurkat cells with TNF-alpha induced a reduction in the levels of cell surface expression of CD28. This effect of TNF-alpha was reversible; however, continuous culture of CD4(+)CD28(+) T cell clones in TNF-alpha resulted in the appearance of a CD28(null) subset. In reporter gene bioassays, TNF-alpha was found to inhibit the activity of the CD28 minimal promoter. Inactivation of the promoter was accompanied by a marked reduction in DNA-protein complex formation by two DNA sequence motifs corresponding to the transcriptional initiator of the CD28 gene. Indeed, in vitro transcription assays showed that nuclear extracts from TNF-alpha-treated cells failed to activate transcription of DNA templates under the control of a consensus TATA box and the CD28 initiator sequences. In contrast, similar extracts from unstimulated T cells supported transcription. These results demonstrate that TNF-alpha directly influences CD28 gene transcription. We propose that the emergence of CD4(+)CD28(null) T cells in vivo is facilitated by increased production of TNF-alpha.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Annexin A5,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
167
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3231-8
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:11544310-Aging,
pubmed-meshheading:11544310-Annexin A5,
pubmed-meshheading:11544310-Antigens, CD28,
pubmed-meshheading:11544310-Apoptosis,
pubmed-meshheading:11544310-Arthritis, Rheumatoid,
pubmed-meshheading:11544310-CD4-Positive T-Lymphocytes,
pubmed-meshheading:11544310-Camptothecin,
pubmed-meshheading:11544310-Cell Line,
pubmed-meshheading:11544310-Cell-Free System,
pubmed-meshheading:11544310-Clone Cells,
pubmed-meshheading:11544310-Down-Regulation,
pubmed-meshheading:11544310-Genes, Reporter,
pubmed-meshheading:11544310-Humans,
pubmed-meshheading:11544310-Jurkat Cells,
pubmed-meshheading:11544310-Lymphocyte Activation,
pubmed-meshheading:11544310-Neoplasm Proteins,
pubmed-meshheading:11544310-Promoter Regions, Genetic,
pubmed-meshheading:11544310-RNA, Messenger,
pubmed-meshheading:11544310-RNA, Neoplasm,
pubmed-meshheading:11544310-T-Lymphocytes,
pubmed-meshheading:11544310-TATA Box,
pubmed-meshheading:11544310-Transcription, Genetic,
pubmed-meshheading:11544310-Tumor Necrosis Factor-alpha
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| pubmed:year |
2001
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| pubmed:articleTitle |
Down-regulation of CD28 expression by TNF-alpha.
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| pubmed:affiliation |
Department of Medicine and Immunology, Mayo Clinic, Rochester, MN 55905, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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