Propofol protects against TNF-α-induced blood-brain barrier disruption via the PIM-1/eNOS/NO pathway.

BACKGROUND The Inflammatory cytokine, tumor necrosis factor-α (TNF-α), disrupts blood-brain barrier (BBB). Propofol reportedly exerts an anti-inflammatory effect in the central nervous system. OBJECTIVE We hypothesized that propofol could provide protective effect against TNF-α-induced disruption in human cerebral microvascular endothelial cells (hCMEC/D3 cells) and explored the underlying mechanisms. METHODS The hCMEC/D3 cell monolayers were pretreated with propofol, followed by TNF-α treatment. The integrity of BBB was reflected by assessing the trans-endothelial electrical resistance (TEER) and determining the expression of pro-teins within tight junctions (TJs). The effect of propofol on TNF-α-modulated nitric oxide production was measured by a nitrate reductase assay kit. The expression of ZO-1, claudin-5, occludin, TNF receptor 1 (TNFR1), TNF receptor 2(TNFR2), proviral-integration site for Moloney murine leukaemia virus (PIM)-1kinase, the phosphorylation of endothelial nitric oxide synthase at ser633(peNOS-ser633) were detected by western blot. RESULTS In hCMEC/D3 cells, TNF-α treatment markedly disrupted the integrity of BBB. Further, we found TNF-α treat-ment could increase the expression of PIM-1, then activate the phosphorylation of eNOS and induce the release of nitric ox-ide (NO). More importantly, we found that TNF-α-impaired BBB integrity could be reversed by propofol. CONCLUSION These results suggest that the PIM-1/eNOS/NO pathway plays a vital role, in which Propofol protects against TNF-α-induced blood-brain barrier disruption.