Nuclear factor-κB 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-kappa B (NF-kappa B), a well-known proinflammatory transcription factor, by visfatin in endothelial cells. RESEARCH DESIGN AND METHODS - Human endothelial cells were transfected with pNF-kappa B-Luc plasmid. Using quantitative PCR, Western blot analysis, and gelatin zymography, we studied NF-kappa B signaling in gelatinase-mediated vascular inflammation by visfatin using the NF-kappa B inhibitor BAY 11-7085. RESULTS - Visfatin significantly increased NF-kappa B transcriptional activity (P < 0.001). We also found a significant inhibition of tumor necrosis factor-alpha JN F-alpha) -induced NF-kappa B activityby visfatin (P < 0.001). Furthermore, the NF-kappa B inhibitor significantly negated visfatin-induced matrix metalloprotemase (MMP)-2/9 mRNA expression, protein levels, and gelatinolytic activity (P < 0.001). CONCLUSIONS - Visfatin-induced NF-kappa B 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.