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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6208
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pubmed:dateCreated |
1989-3-28
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pubmed:abstractText |
Tumour necrosis factor-alpha (TNF-alpha) is secreted by macrophages in response to inflammation, infection and cancer. Sublethal doses of recombinant TNF-alpha to rats causes cachexia, anaemia and inflammation. TNF-alpha plays a major part in tissue inflammation and remodelling by stimulating production of collagenase. Cellular responses to TNF-alpha are initiated by binding to high-affinity cell surface receptors. TNF-alpha then profoundly affects gene regulation, stimulating the fos, myc, interleukin-1 and interleukin-6 genes and inhibiting the type I collagen gene. Here we demonstrate that TNF-alpha also stimulates collagenase gene transcription; this stimulation is mediated by an element of the gene that is responsive to the transcription factor AP-1, the major component of which (jun/AP-1) is encoded by the jun gene; and that TNF-alpha stimulates prolonged activation of jun gene expression. This prolonged induction of jun contrasts with its transient activation by the phorbol ester TPA and provides a physiological example of the ability of jun/AP-1 to stimulate its own transcription. This may be a key mechanism for mediating at least some of the biological effects of TNF-alpha.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0028-0836
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
337
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
661-3
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:2537468-Blotting, Northern,
pubmed-meshheading:2537468-Cells, Cultured,
pubmed-meshheading:2537468-Chloramphenicol O-Acetyltransferase,
pubmed-meshheading:2537468-DNA-Binding Proteins,
pubmed-meshheading:2537468-Fibroblasts,
pubmed-meshheading:2537468-Gene Expression Regulation,
pubmed-meshheading:2537468-Genes,
pubmed-meshheading:2537468-Humans,
pubmed-meshheading:2537468-Microbial Collagenase,
pubmed-meshheading:2537468-Protein Kinase C,
pubmed-meshheading:2537468-Proto-Oncogene Proteins,
pubmed-meshheading:2537468-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:2537468-Proto-Oncogenes,
pubmed-meshheading:2537468-RNA, Messenger,
pubmed-meshheading:2537468-Transcription, Genetic,
pubmed-meshheading:2537468-Transcription Factors,
pubmed-meshheading:2537468-Tumor Necrosis Factor-alpha
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pubmed:year |
1989
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pubmed:articleTitle |
Prolonged activation of jun and collagenase genes by tumour necrosis factor-alpha.
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pubmed:affiliation |
Department of Medicine, University of California at San Diego, School of Medicine, La Jolla 92093.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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