Nuclear Factor-κB Induction by Visfatin in Human Vascular Endothelial Cells
Its role in MMP-2/9 production and activation
- Raghu Adya, MBBS, MSC,
- Bee K. Tan, MBBS,
- Jing Chen, PHD and
- Harpal S. Randeva, MBCHB, FRCP, MD, PHD
- From the Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, U.K.
- Address correspondence and reprint requests to Dr. Harpal S. Randeva, MBCHB, FRCP, MD, PhD, Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, U.K. E-mail: harpal.randeva{at}warwick.ac.uk
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.
- HUVEC, human umbilical vein endothelial cell
- MMP, matrix metalloproteinase
- NF-κB, nuclear factor-κB
- TNF-α, tumor necrosis factor-α
Footnotes
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Published ahead of print at http://care.diabetesjournals.org on 9 January 2008. DOI: 10.2337/dc07-1544.
Additional information for this article can be found in an online appendix at http://dx.doi.org/10.2337/dc07-1544.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.
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- Accepted December 25, 2007.
- Received August 6, 2007.
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