Nuclear Factor-κB Induction by Visfatin in Human Vascular Endothelial Cells

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