title: TNFα enhances TLR3-dependent effects on MMP-9 expression in human mesangial cells.
abstract: The role of MMPs (matrix metalloproteinases) in kidney diseases has been widely accepted, where they can regulate inflammatory response because of their effects on both recruitment and survival of inflammatory cells. TNFα (tumour necrosis factor α) has also been implicated in the pathogenesis of inflammatory kidney diseases, including forms of glomerulonephritis associated with viral diseases. Previously, we established the functional linkage between viral receptors of the innate immune system, the TLRs (Toll-like receptors) and control of MMP activity in human MC (mesangial cells). Expression levels of MMP-2, MMP-7, MMP-9, TIMP-1 (tissue inhibitor of metalloproteinase 1) and TIMP-2 in human MC in culture were analysed by RT-PCR (reverse transcription-PCR). TNFα significantly enhanced the TLR3-dependent induction of MMP-9 in human MC. Expression levels of MMP-2, TIMP-1 and TIMP-2 were not significantly affected by the activation of TLR3 or TNFα stimulation. No significant MMP-7 expression was found. We conclude that the role of MMP-9 in chemotaxis, activation and proliferation of inflammatory cells is amplified by TNFα originating from infiltrating cells, especially monocytes, producing a regulatory loop that potentially leads to a self-propagating inflammation.
authors.affiliation: Medizinische Klinik und Poliklinik IV-Campus Innenstadt, Klinikum der LMU, Munich, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Merkle
authors.forename: Andrea
authors.initials: A
authors.lastname: Ribeiro
authors.forename: Simone
authors.initials: S
authors.lastname: Köppel
authors.forename: Markus
authors.initials: M
authors.lastname: Wörnle
mesh_terms: D002460:Cell Line; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology / Q000821:virology; D006801:Humans; D007369:Interferon Inducers / Q000276:immunology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000276:immunology; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000276:immunology; D050527:Mesangial Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D011070:Poly I-C / Q000276:immunology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000276:immunology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D007369:Interferon Inducers; C495344:TLR3 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D051196:Toll-Like Receptor 3; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D011070:Poly I-C