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

Abstract

Abstract. 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.

Propofol attenuates intermittent hypoxia induced up-regulation of proinflammatory cytokines in microglia through inhibiting the activation of NF-Bκ/p38 MAPK signalling

“…A recent report clarified that triroside attenuated the neuroinflammation in microglia via NF-κB and p38 MAPK signalling pathways [28]. Furthermore, propofol suppressed the NF-κB-mediated inflammation by prohibiting the activation of p38 MAPK in IH-treated vascular endothelium [16]. Consistently with previous reports, IH-induced activation of NF-κB and p38 MAPK both were dramatically reduced by propofol treatment in the present study.…”

“…A wealth of information linking that propofol prohibited inflammatory response through preventing the NF-κB and p38 MAPK signalling and then reducing the release of inflammatory mediators is published [25,26]. In addition, emerging evidence showed that propofol selectively attenuated the activation of NF-κB and p38 MAPK in vascular endothelium during IH exposure [16]. The effect of propofol on IH treated microglia was still unclear.…”

“…Consequently, NF-κB will be disassociated from IκB and translocate into nucleus, followed by the activation of NF-κB-dependent proinflammatory molecules [6,7]. It has been demonstrated that propofol suppresses the IH-induced NF-κB activity by preventing the phosphorylation of IκB and accompanied by down-regulated secretion of proinflammatory cytokines in the vascular endothelial cells [16].…”

The Effects of Two Anesthetics, Propofol and Sevoflurane, on Liver Ischemia/Reperfusion Injury

“…The PI3K/Akt and p38 MAPK pathway exists extensively in cells and is involved in the regulation of a series of physiological activities such as cell apoptosis. Both propofol and sevoflurane were reported to regulate AKT and p38 expression levels [47][48][49]; however, this phenomenon was not observed in our study. As expected, propofol increased the phosphorylation of AKT but decreased the phosphorylation of Bad, while no changes were detected in the expression or phosphorylation of p38.…”

Propofol up-regulates expression of ABCA1, ABCG1, and SR-B1 through the PPARγ/LXRα signaling pathway in THP-1 macrophage-derived foam cells

“…In addition, propofol demonstrates anti-inflammatory properties by decreasing the production of proinflammatory cytokines, including tumor necrosis factor-alpha and interleukins 1, 6, 8, and 10; inhibits neutrophil chemotaxis, cellular attachment and migration, phagocytosis, production of inducible nitric oxide synthase, and reactive oxygen species; scavenges free radicals; decreases lipid peroxidation; and inhibits platelet aggregation [26,29]. Li et al [30] reported that propofol may have the potential to prevent atherosclerosis in patients by inhibiting nuclear factor-κB (NF-κB)-mediated inflammation in the vascular endothelium. In addition, Hsing et al [31] demonstrated that propofol decreased NF-κB, but increased PPARγ, expression in lipopolysaccharide stimulated rat mesangial cells.…”