Tumor necrosis factor-alpha enhances hyperbaric oxygen-induced visfatin expression via JNK pathway in human coronary arterial endothelial cells

Visfatin, a adipocytokine with insulin-mimetic effect, plays a role in endothelial angiogenesis. Hyperbaric oxygen (HBO) has been used in medical practice.

However, the molecular mechanism of beneficial effects of HBO is poorly understood. We sought to investigate the cellular and molecular mechanisms of regulation of visfatin by HBO in human coronary arterial endothelial cells (CAECs).

Methods: Human CAECs were exposed to 2.5 atmosphere absolute (ATA) of oxygen in a hyperbaric chamber. Western blot, real-time polymerase chain reaction, and promoter activity assay were performed.

In vitro glucose uptake and tube formation was detected.

Results: Visfatin protein (2.55-fold) and mRNA (2.53-fold) expression were significantly increased after exposure to 2.5 ATA HBO for 4 to 6 h. Addition of SP600125 and JNK siRNA 30 min before HBO inhibited the induction of visfatin protein.

HBO also significantly increased DNA-protein binding activity of AP-1 and visfatin promoter activity. Addition of SP600125 and TNF-alpha monoclonal antibody 30 min before HBO abolished the DNA-protein binding activity and visfatin promoter activity induced by HBO.

HBO significantly increased secretion of TNF-alpha from cultured human CAECs. Exogenous addition of TNF-alpha significantly increased visfatin protein expression while TNF- antibody and TNF-alpha receptor antibody blocked the induction of visfatin protein expression induced by HBO.

HBO increased glucose uptake in human CAECs as HBO and visfatin siRNA and TNF-alpha antibody attenuated the glucose uptake induced by HBO. HBO significantly increased the tube formation of human CAECs while visfatin siRNA, TNF-alpha antibody inhibited the tube formation induced by HBO.

Conclusions: HBO activates visfatin expression in cultured human CAECs.

HBO-induced visfatin is mediated by TNF-alpha and at least in part through JNK pathway.

Author: Bao-Wei WangChiu-Mei LinGong-Jhe WuKou-Gi Shyu
Credits/Source: Journal of Biomedical Science 2011, 18:27

Published on: 2011-05-04

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