期刊
TOXICOLOGY IN VITRO
卷 25, 期 8, 页码 1834-1840出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2011.09.024
关键词
Tetrandrine; ERK; NF-kappa B; NO; MMP-9; Mesangial cell
类别
资金
- National Science Council of Taiwan [NSC95-2320-B-195-003-MY2]
- Mackay Memorial Hospital [MMH-9828, MMH-9974]
Objectives: Tetrandrine (TET), a bisbenzylisoquinoline alkaloid isolated from Stephania tetrandra S. Moore of the Menispermaceae, possesses anti-inflammatory activity. We examined the effect of tetrandrine on interleukin-1 beta (IL-1 beta)-provoked inflammatory response in mesangial cells. Materials and methods: Primary rat mesangial cells (PRMCs) were treated with IL-1 beta to induce inflammation to resemble glomerulonephritis. Cell viability, morphology and NO production were evaluated. Western blotting was applied for expression of matrix metalloproteinase-9 (MMP-9), inducible NO synthase (iNOS), extracellular signal-regulated kinase (ERK) and NF-kappa B-related molecules. Electrophoretic mobility shift assay was performed to examine the DNA-binding activity of NF-kappa B. Results: TET, at concentrations up to 10 mu g/ml, had no significant effect on viability of PRMCs. At nontoxic concentrations, TET inhibited expression of phosphorylated ERK as well as phosphorylated IKK, enhanced degradation of I kappa B alpha, and reduced the DNA-binding activity of NF-kappa B in IL-1 beta-primed PRMCs, suggesting an inhibitory effect on ERK/NF-kappa B signaling. TET attenuated the IL-1 beta-provoked expression of iNOS and release of NO. Moreover, both the protein expression and gelatinase activity of MMP-9, but not MMP-2, were markedly suppressed by TET. Significance: TET down-regulated ERK/NF-kappa B signaling and inhibited the expression of inflammatory mediators NO and MMP-9. Since these mediators appear to activate mesangial cells, TET may play an important role in prevention of glomerulonephritis. (C) 2011 Elsevier Ltd. All rights reserved.
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