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 a 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 proteins 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 treatment could increase the expression of PIM-1, then activate the phosphorylation
of eNOS and induce the release of nitric oxide (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.
Microglia-derived TNF-α mediates endothelial necroptosis aggravating blood brain–barrier disruption after ischemic stroke
