Interleukin 15 stimulates production of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 by human peripheral blood mononuclear cells.
In peripheral blood mononuclear cells (PBMC), matrix metalloproteinase (MMP)-9 mediates the extravasation of immune cells and may be involved in tissue destruction during inflammation. We investigated the effect of the pro-inflammatory cytokines interleukin (IL-)12 and 15 on the secretion of MMP-9 in PBMC. IL-15, but not IL-12, induces MMP-9 in PBMC and in T cells. Moreover, the combination of IL-15 and IL-2 had an additive effect. In contrast, both IL-12 and IL-15 induced the release of tissue inhibitor of metalloproteinases (TIMP)-1. IL-15 led to a dose-dependent increase of the MMP-9/TIMP-1 ratio as a measure for increased proteolytic capacity. We conclude that IL-15 mediates its effects in inflammation in part through MMP-9.
Departments of Neurology and Research, University Hospital, Basle, Switzerland.
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CS
Constantinescu
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Grygar
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Kappos
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Leppert
D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D004792:Enzyme Precursors / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000276:immunology; D008213:Lymphocyte Activation; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000096:biosynthesis*
D004792:Enzyme Precursors; D019409:Interleukin-15; D019715:Tissue Inhibitor of Metalloproteinase-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9