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-alpha (TNF-alpha) 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-alpha. The expression and phosphorylation of Hif-1 alpha, 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-alpha (10ng/ml, 4h) significantly decreased the expression of occludin, which was attenuated by propofol (25 mu M). TNF-alpha induced Hif-1 alpha/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-alpha induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1 alpha, VEGFR-2, and ERK could reduce the effect of TNF-alpha on occludin expression.ConclusionTNF-alpha could decrease the expression of occludin via activating Hif-1 alpha/ VEGF/ VEGFR-2/ ERK signaling pathway, which was attenuated by propofol.
[1]Fudan Univ, Shanghai Canc Ctr, Dept Anesthesiol, Shanghai 200032, Peoples R China;
[2]Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
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