title: Tetrandrine down-regulates ERK/NF-κB signaling and inhibits activation of mesangial cells.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Nephrology, Mackay Memorial Hospital, and Department of Pharmacology, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
authors: Chih-Jen
authors: CJ
authors: Wu
authors: Yi-Hsuan
authors: YH
authors: Wang
authors: Cheng-Jui
authors: CJ
authors: Lin
authors: Han-Hsiang
authors: HH
authors: Chen
authors: Yu-Jen
authors: YJ
authors: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D044182:Benzylisoquinolines; D053583:Interleukin-1beta; D016328:NF-kappa B; C009438:tetrandrine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020780:Matrix Metalloproteinase 9