科研之友
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摘要
Background: Mesangial cells are known to secrete metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) that are capable of disrupting the glomerular basement membrane (GBM). Disruption of the GBM appears to be an important mechanism in the renal disease process, however little is known about the mechanisms involved. Therefore we examined the potential role of nitric oxide (NO) in the regulation of MMP-9 and TIMP-1 by tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) using the human mesangial cell line (HMCL). Methods: The HMCL was treated with various concentrations of cytokines and NO inhibitors. Activity of MMP-9 was examined by gelatin zymography and TIMP-1 expression was analysed by Western blotting. NO production was measured using the Greiss assay. Results: In this study, stimulation of HMCL cells with TNF-alpha or IL-1 beta, alone or in combination, led to a substantial increase in NO production, which was shown to result from an increase in the expression of the inducible form of NOS (iNOS). Treatment of cells with the specific iNOS inhibitor L-NIL potentiated the increase in MMP-9 production induced by TNF-alpha, but prevented the suppression of TIMP-1 production observed following cytokine treatment. The NO donor, sodium nitroprusside, also stimulated a substantial increase in NO production in HMCL cells, which was associated with a reduction in basal and TNF-alpha-stimulated MMP-9 and a potentiation of the cytokine-induced decrease in TIMP-1. Conclusions: Our study provides convincing evidence of a modulatory role for NO on cytokine-induced MMP-9 and TIMP-1 production in human mesangial cells.
- 出版日期2008
