Linked Life Data

12616343

Source:http://linkedlifedata.com/resource/pubmed/id/12616343

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pubmed-article:12616343pubmed:dateCreated2003-3-4lld:pubmed
pubmed-article:12616343pubmed:abstractTextThe 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.lld:pubmed
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pubmed-article:12616343pubmed:authorpubmed-author:EberhardtWolf...lld:pubmed
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pubmed-article:12616343pubmed:authorpubmed-author:MühlHeikoHlld:pubmed
pubmed-article:12616343pubmed:authorpubmed-author:GoedeAndreasAlld:pubmed
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pubmed-article:12616343pubmed:volume367lld:pubmed
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pubmed-article:12616343pubmed:pagination68-75lld:pubmed
pubmed-article:12616343pubmed:dateRevised2006-11-15lld:pubmed
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pubmed-article:12616343pubmed:articleTitleIL-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.lld:pubmed
pubmed-article:12616343pubmed:affiliationPharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.lld:pubmed
pubmed-article:12616343pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:12616343pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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