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硫化氢减轻肿瘤坏死因子-α诱导的血管内皮细胞炎症信号和功能障碍。

Hydrogen sulfide attenuated tumor necrosis factor-α-induced inflammatory signaling and dysfunction in vascular endothelial cells.

机构信息

Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, China.

出版信息

PLoS One. 2011 May 10;6(5):e19766. doi: 10.1371/journal.pone.0019766.

DOI:10.1371/journal.pone.0019766
PMID:21572963
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3091882/
Abstract

BACKGROUND

Hydrogen sulfide (H(2)S), the third physiologically relevant gaseous molecule, is recognized increasingly as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the effects and mechanisms of sodium hydrosulfide (NaHS, a H(2)S donor) on tumor necrosis factor (TNF)-α-induced human umbilical vein endothelial cells (HUVEC) dysfunction.

METHODOLOGY AND PRINCIPAL FINDINGS

Application of NaHS concentration-dependently suppressed TNF-α-induced mRNA and proteins expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), mRNA expression of P-selectin and E-selectin as well as U937 monocytes adhesion to HUVEC. Western blot analysis revealed that the expression of the cytoprotective enzyme, heme oxygenase-1 (HO-1), was induced and coincident with the anti-inflammatory action of NaHS. Furthermore, TNF-α-induced NF-κB activation assessed by IκBα degradation and p65 phosphorylation and nuclear translocation and ROS production were diminished in cells subjected to treatment with NaHS.

SIGNIFICANCE

H(2)S can exert an anti-inflammatory effect in endothelial cells through a mechanism that involves the up-regulation of HO-1.

摘要

背景

硫化氢(H₂S),第三种具有生理相关性的气体分子,在各种炎症情况下,作为一种抗炎介质,其作用正得到越来越多的认可。在此,我们研究了氢硫化钠(NaHS,一种 H₂S 供体)对肿瘤坏死因子(TNF)-α诱导的人脐静脉内皮细胞(HUVEC)功能障碍的影响及其作用机制。

方法和主要发现

NaHS 的浓度依赖性抑制 TNF-α诱导的细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)mRNA 和蛋白表达、P-选择素和 E-选择素 mRNA 表达以及 U937 单核细胞黏附到 HUVEC。Western blot 分析显示,保护酶血红素加氧酶-1(HO-1)的表达被诱导,且与 NaHS 的抗炎作用一致。此外,NaHS 处理的细胞中 TNF-α诱导的 NF-κB 激活,表现为 IκBα 降解和 p65 磷酸化以及核转位和 ROS 产生减少。

意义

H₂S 通过上调 HO-1 在血管内皮细胞中发挥抗炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c38d/3091882/dcf63932b18c/pone.0019766.g007.jpg
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