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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6490
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pubmed:dateCreated |
1994-9-6
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pubmed:abstractText |
Tumour necrosis factor-alpha (TNF-alpha) is a potent pro-inflammatory and immunomodulatory cytokine implicated in inflammatory conditions such as rheumatoid arthritis, Crohn's disease, multiple sclerosis and the cachexia associated with cancer or human immunodeficiency virus infection. TNF-alpha is initially expressed as a 233-amino-acid membrane-anchored precursor which is proteolytically processed to yield the mature, 157-amino-acid cytokine. The processing enzyme(s) which cleave TNF-alpha are unknown. Here we show that the release of mature TNF-alpha from leukocytes cultured in vitro is specifically prevented by synthetic hydroxamic acid-based metalloproteinase inhibitors, which also prevent the release of TNF-alpha into the circulation of endotoxin challenged rats. A recombinant, truncated TNF-alpha precursor is cleaved to biologically active, mature TNF-alpha by several matrix metalloproteinase enzymes. These results indicate that processing of the TNF-alpha precursor is dependent on at least one matrix metalloproteinase-like enzyme, inhibition of which represents a novel therapeutic mechanism for interfering with TNF-alpha production.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0028-0836
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
18
|
pubmed:volume |
370
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
N
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pubmed:pagination |
555-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8052310-Animals,
pubmed-meshheading:8052310-Cells, Cultured,
pubmed-meshheading:8052310-Humans,
pubmed-meshheading:8052310-Hydroxamic Acids,
pubmed-meshheading:8052310-Leukocytes,
pubmed-meshheading:8052310-Male,
pubmed-meshheading:8052310-Metalloendopeptidases,
pubmed-meshheading:8052310-Protein Processing, Post-Translational,
pubmed-meshheading:8052310-Rats,
pubmed-meshheading:8052310-Rats, Sprague-Dawley,
pubmed-meshheading:8052310-Recombinant Fusion Proteins,
pubmed-meshheading:8052310-Tumor Necrosis Factor-alpha
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pubmed:year |
1994
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pubmed:articleTitle |
Processing of tumour necrosis factor-alpha precursor by metalloproteinases.
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pubmed:affiliation |
British Biotech, Cowley, Oxford, UK.
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pubmed:publicationType |
Journal Article
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