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TNFα enhances TLR3‐dependent effects on MMP‐9 expression in human mesangial cells
Author(s) -
Merkle Monika,
Ribeiro Andrea,
Köppel Simone,
Wörnle Markus
Publication year - 2012
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1042/cbi20120282
Subject(s) - tlr3 , matrix metalloproteinase , inflammation , innate immune system , tumor necrosis factor alpha , biology , microbiology and biotechnology , immune system , receptor , chemotaxis , chemokine , immunology , cancer research , tissue inhibitor of metalloproteinase , toll like receptor , biochemistry
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.