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Toxicol In Vitro. 2011 Dec;25(8):1834-40. doi: 10.1016/j.tiv.2011.09.024. Epub 2011 Oct 7.

Tetrandrine down-regulates ERK/NF-κB signaling and inhibits activation of mesangial cells.

Author information

1
Department of Nephrology, Mackay Memorial Hospital, and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.

Abstract

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-1β (IL-1β)-provoked inflammatory response in mesangial cells.

MATERIALS AND METHODS:

Primary rat mesangial cells (PRMCs) were treated with IL-1β 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-κB-related molecules. Electrophoretic mobility shift assay was performed to examine the DNA-binding activity of NF-κB.

RESULTS:

TET, at concentrations up to 10 μg/ml, had no significant effect on viability of PRMCs. At non-toxic concentrations, TET inhibited expression of phosphorylated ERK as well as phosphorylated IKK, enhanced degradation of IκBα and reduced the DNA-binding activity of NF-κB in IL-1β-primed PRMCs, suggesting an inhibitory effect on ERK/NF-κB signaling. TET attenuated the IL-1β-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-κB 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.

PMID:
22001142
DOI:
10.1016/j.tiv.2011.09.024
[Indexed for MEDLINE]

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