Source:http://linkedlifedata.com/resource/pubmed/id/12616343
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rdf:type | |
lifeskim:mentions |
umls-concept:C0030685,
umls-concept:C0040300,
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umls-concept:C0331858,
umls-concept:C0383327,
umls-concept:C0391871,
umls-concept:C0392760,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1456820,
umls-concept:C1548602,
umls-concept:C1704640,
umls-concept:C1706515,
umls-concept:C1706968,
umls-concept:C1709059,
umls-concept:C1963578,
umls-concept:C1999216,
umls-concept:C2243049
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pubmed:issue |
1
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pubmed:dateCreated |
2003-3-4
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pubmed:abstractText |
The proinflammatory cytokine interleukin (IL)-18 appears to be involved in the etiology of a variety of pathological conditions, among them rheumatoid arthritis and atherosclerosis as well as tumor growth and metastasis. As biological activity of matrix metalloproteinase-9 (MMP-9) has been identified as a hallmark in the pathogenesis of these diseases, effects of IL-18 on MMP-9 production by human peripheral blood mononuclear cells (PBMC) were investigated. Moreover, effects of immunopharmacological intervention by anti-tumor necrosis factor-alpha (TNFalpha) or IL-10 were evaluated. Here we report that IL-18 augmented production of MMP-9 by PBMC. The potency of IL-18 to induce release of MMP-9 from PBMC was comparable with that of TNFalpha. MMP-9 production was dependent on endogenous production of TNFalpha, as detected by use of neutralizing monoclonal antibodies. Whereas IL-18 and TNFalpha induced the protease, MMP-9 release was not mediated by IFNgamma. IL-18 also induced secretion of MMP-9 from human whole blood cultures. Antiinflammatory IL-10 efficiently downregulated release of MMP-9 from unstimulated and IL-18-activated PBMC. In contrast to MMP-9, secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) was not augmented by IL-18. Addition of IL-10 enhanced release of TIMP-1 from PBMC. The present study broadens the current pattern of IL-18 proinflammatory actions on PBMC, emphasizes the pivotal role of intermediate TNFalpha production in these responses, and relates IL-18 biological functions to the pathological role of MMP-9.
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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/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Inhibitor of...,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0028-1298
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
367
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
68-75
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12616343-Gene Expression Regulation,
pubmed-meshheading:12616343-Humans,
pubmed-meshheading:12616343-Inflammation Mediators,
pubmed-meshheading:12616343-Interleukin-10,
pubmed-meshheading:12616343-Interleukin-18,
pubmed-meshheading:12616343-Leukocytes, Mononuclear,
pubmed-meshheading:12616343-Matrix Metalloproteinase 9,
pubmed-meshheading:12616343-Recombinant Proteins,
pubmed-meshheading:12616343-Tissue Inhibitor of Metalloproteinase-1,
pubmed-meshheading:12616343-Tumor Necrosis Factor-alpha
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pubmed:year |
2003
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pubmed:articleTitle |
IL-18 initiates release of matrix metalloproteinase-9 from peripheral blood mononuclear cells without affecting tissue inhibitor of matrix metalloproteinases-1: suppression by TNF alpha blockage and modulation by IL-10.
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pubmed:affiliation |
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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