Propofol selectively inhibits nuclear factor-κB activity by suppressing p38 mitogen-activated protein kinase signaling in human EA.hy926 endothelial cells during intermittent hypoxia/reoxygenation.

Intermittent hypoxia/reoxygenation (IHR) induces proinflammatory cytokines, contributing to the pathogenic process of atherosclerosis associated with obstructive sleep apnea (OSA). Two transcription factors, nuclear factor-κB (NF-κB) and hypoxia-inducible factor-1 (HIF-1), have been indicated to mediate proinflammatory cytokines during IHR. The anti-inflammatory effects of propofol have attracted increasing attention in regard to the treament of multiple diseases associated with inflammation. The present study examined whether propofol inhibits NF-κB and HIF-1 activity in vascular endothelial cells during IHR. EA.hy926 endothelial cells were exposed to IHR for 64 cycles with or without propofol treatment. Gene knockdown by transfection of siRNA against p38 mitogen-activated protein kinase (MAPK) was also used to investigate the molecular mechanisms. Compared with the control group, IHR exposure significantly induced the activation of NF-κB and HIF-1, enhanced the mRNA expression of proinflammatory cytokines and increased the activation of p38 MAPK. Propofol dose-dependently inhibited the IHR‑induced activation of NF-κB, but did not change the activation of HIF-1, which was accompanied by decreased levels of proinflammatory cytokines. In addition, IHR‑induced p38 MAPK activity was attenuated by propofol in a similar manner to the reduction in NF-κB activity. Furthermore, knockdown of p38 MAPK with siRNA significantly reduced the IHR‑induced activation of NF-κB, while not affecting HIF-1. These data demonstrate that propofol selectively attenuates the IHR‑induced activation of NF-κB, but not HIF-1, in vascular endothelial cells, and these beneficial effects are likely to be based on the inhibition of the p38 MAPK signaling pathway. Propofol may have the potential to prevent atherosclerosis in patients with OSA by inhibiting NF-κB‑mediated inflammation in the vascular endothelium.