title: Nuclear factor-kappaB induction by visfatin in human vascular endothelial cells: its role in MMP-2/9 production and activation.
abstract: OBJECTIVE
  Visfatin is elevated in obesity and type 2 diabetes and is thought to be an inflammatory mediator within atherosclerotic lesions and to induce gelatinase activity. We investigated the activation of nuclear factor-kappaB (NF-kappaB), a well-known proinflammatory transcription factor, by visfatin in endothelial cells.
  
  
  METHODS
  Human endothelial cells were transfected with pNF-kappaB-Luc plasmid. Using quantitative PCR, Western blot analysis, and gelatin zymography, we studied NF-kappaB signaling in gelatinase-mediated vascular inflammation by visfatin using the NF-kappaB inhibitor BAY 11-7085.
  
  
  RESULTS
  Visfatin significantly increased NF-kappaB transcriptional activity (P < 0.001). We also found a significant inhibition of tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappaB activity by visfatin (P < 0.001). Furthermore, the NF-kappaB inhibitor significantly negated visfatin-induced matrix metalloproteinase (MMP)-2/9 mRNA expression, protein levels, and gelatinolytic activity (P < 0.001).
  
  
  CONCLUSIONS
  Visfatin-induced NF-kappaB signaling in human endothelial cells affects the activation of gelatinases MMP-2 and -9, suggesting an important role of visfatin in the pathogenesis of vascular inflammation in obesity and type 2 diabetes.
authors.affiliation: Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Raghu
authors.initials: R
authors.lastname: Adya
authors.forename: Bee K
authors.initials: BK
authors.lastname: Tan
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Harpal S
authors.initials: HS
authors.lastname: Randeva
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D007700:Kinetics; D008156:Luciferases / Q000235:genetics; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism / Q000494:pharmacology*; D009765:Obesity / Q000201:enzymology; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D016328:NF-kappa B; D008156:Luciferases; D054409:Nicotinamide Phosphoribosyltransferase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9