Nuclear factor-kappaB induction by visfatin in human vascular endothelial cells: its role in MMP-2/9 production and activation.

Abstract

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. 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. 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). 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.