Abstract
BackgroundThe levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). It has been reported that propofol, the most commonly used anesthetic, could inhibit inflammation response in CNS. In this study, we investigated the effects of tumor necrosis factor-α (TNF-α) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms.MethodsThe hCMEC/D3 cells were treated with propofol, followed by TNF-α. The expression and phosphorylation of Hif-1α, VEGF, VEGFR-2, ERK, p38MAPK and occludin were measured by Western blot analysis. The cell viability of hCMEC/D3 cells was measured by cell counting kit-8.ResultsTNF-α (10 ng/ml, 4 h) significantly decreased the expression of occludin, which was attenuated by propofol (25 μM). TNF-α induced Hif-1α/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-α induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1α, VEGFR-2, and ERK could reduce the effect of TNF-α on occludin expression.ConclusionTNF-α could decrease the expression of occludin via activating Hif-1α/ VEGF/ VEGFR-2/ ERK signaling pathway, which was attenuated by propofol.
Highlights
The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS)
tumor necrosis factor-α (TNF-α) decreased the expression of occludin in Human cerebral microvascular endothelial cell (hCMEC)/D3 cells
It is noted that 10 ng/ml was the minimal dose of TNF-α to exert significant effect on occludin expression
Summary
The levels of tight junction proteins (TJs), especially occludin, correlate with blood-brain barrier (BBB) disruption caused by inflammation in central nervous system (CNS). Blood-brain barrier (BBB) is a multicellular structure and mainly consists of microvascular endothelial cells, astrocytes, pericytes, intercellular tight junctions and basal lamina [1]. One of the most important components of BBB, are linked together through multiple tight junction proteins including claudins, occludin and zonula occludens (ZOs) [5]. It has been reported that the decreased expression of tight junction proteins, especially occludin, correlates with the disruption of BBB [6, 7]. A study revealed that truncation of occludin decreased transendothelial electrical resistance, suggesting a key role of occludin in the barrier function of BBB [8]
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