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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0006556,
umls-concept:C0007301,
umls-concept:C0014442,
umls-concept:C0017262,
umls-concept:C0086418,
umls-concept:C0185117,
umls-concept:C0204727,
umls-concept:C0205177,
umls-concept:C0205409,
umls-concept:C0851285,
umls-concept:C0887824,
umls-concept:C1456820,
umls-concept:C1706637,
umls-concept:C2911684
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pubmed:issue |
9
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pubmed:dateCreated |
1998-5-21
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pubmed:databankReference | |
pubmed:abstractText |
A snake venom-like protease isolated by a differential display screen between normal and osteoarthritis (OA)-affected cartilage (designated as cSVP) has a cDNA sequence identical to TNF-alpha convertase enzyme (TACE). TACE shows the presence of an unknown prodomain, a cysteine switch, a catalytic domain, a zinc binding region, a disintegrin region, an EGF-like domain, a transmembrane domain, and a unique cytoplasmic region. A TACE construct harboring the signal + prodomain + catalytic region (TACE-SPCdeltaDETCy), expressed in baculovirus could cleave preferentially (approximately 12-fold) the TNF-specific peptide over the matrix metalloproteases peptide in vitro. This recombinant protein also cleaved the natural substrate GST-ProTNF-alpha to TNF-alpha (17 kDa) in vitro. The mRNA for TACE, which is broadly distributed and differentially expressed in a variety of human tissues, is up-regulated in arthritis-affected cartilage, but not normal cartilage. OA-affected cartilage also expressed TNF-alpha mRNA that was not detected in normal cartilage. The OA-affected cartilage (in explant assays) spontaneously released TNF-alpha and IL-8 in ex vivo conditions. Addition of TNF-alphaR fused to IgG Fc fragment (TNF-alphaR:Fc) in the presence or absence of soluble IL-1R (with which it acted additively) significantly attenuated the spontaneous/autocrine release of articular IL-8 in this assay. These experiments demonstrate a functional paracrine/autocrine role of TNF-alpha in OA-affected cartilage that may depend, in part, on up-regulated levels of chondrocyte-derived TACE.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ADAM Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/tumor necrosis factor-alpha...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
160
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4570-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9574564-ADAM Proteins,
pubmed-meshheading:9574564-Arthritis, Rheumatoid,
pubmed-meshheading:9574564-Cartilage,
pubmed-meshheading:9574564-Cloning, Molecular,
pubmed-meshheading:9574564-DNA, Complementary,
pubmed-meshheading:9574564-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:9574564-Humans,
pubmed-meshheading:9574564-Metalloendopeptidases,
pubmed-meshheading:9574564-Molecular Sequence Data,
pubmed-meshheading:9574564-Organ Culture Techniques,
pubmed-meshheading:9574564-Sequence Analysis,
pubmed-meshheading:9574564-Tumor Necrosis Factor-alpha
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pubmed:year |
1998
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pubmed:articleTitle |
TNF-alpha convertase enzyme from human arthritis-affected cartilage: isolation of cDNA by differential display, expression of the active enzyme, and regulation of TNF-alpha.
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pubmed:affiliation |
Department of Rheumatology and Medicine, Hospital for Joint Diseases, New York, NY 10003, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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