Dataset Information

Propofol attenuated TNF-?-modulated occludin expression by inhibiting Hif-1?/ VEGF/ VEGFR-2/ ERK signaling pathway in hCMEC/D3 cells.

ABSTRACT:

Background

The 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-? (TNF-?) and propofol on occludin expression in human cerebral microvascular endothelial cell line, D3 clone (hCMEC/D3 cells), and explored the underlying mechanisms.

Methods

The hCMEC/D3 cells were treated with propofol, followed by TNF-?. The expression and phosphorylation of Hif-1?, 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.

Results

TNF-? (10?ng/ml, 4?h) significantly decreased the expression of occludin, which was attenuated by propofol (25??M). TNF-? induced Hif-1?/VEGF/VEGFR-2/ERK signaling pathway, while propofol could inhibit it. TNF-? induced the phosphorylation of p38MAPK, while propofol had no effect on it. In addition, the inhibitors of Hif-1?, VEGFR-2, and ERK could reduce the effect of TNF-? on occludin expression.

Conclusion

TNF-? could decrease the expression of occludin via activating Hif-1?/ VEGF/ VEGFR-2/ ERK signaling pathway, which was attenuated by propofol.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6617648 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Propofol attenuated TNF-α-modulated occludin expression by inhibiting Hif-1α/ VEGF/ VEGFR-2/ ERK signaling pathway in hCMEC/D3 cells.

Zhang Yue Y Ding Xiaowei X Miao Changhong C Chen Jiawei J

BMC anesthesiology 20190709 1

<h4>Background</h4>The 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 cell ...[more]

PMID: 31288745

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