Nuclear factor-kappaB induction by visfatin in human vascular endothelial cells: its role in MMP-2/9 production and activation.
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.
Adya
Raghu
R
Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Tan
Bee K
BK
Chen
Jing
J
Randeva
Harpal S
HS
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
D016328:NF-kappa B; D008156:Luciferases; D054409:Nicotinamide Phosphoribosyltransferase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9