Resolvin D1 Reverts Lipopolysaccharide-Induced TJ Proteins Disruption and the Increase of Cellular Permeability by Regulating IκBαSignaling in Human Vascular Endothelial Cells

Xingcai Zhang,Wanli Xie,Ping Gui,Tingting Wang,Shanglong Yao,Chengye Yao,Wei Sun,Huiqing Wang,Linlin Wang,Yun Lin,Qingping Wu

doi:10.1155/2013/185715

Abstract

Tight Junctions (TJ) are important components of paracellular pathways, and their destruction enhances vascular permeability. Resolvin D1 (RvD1) is a novel lipid mediator that has treatment effects on inflammatory diseases, but its effect on inflammation induced increase in vascular permeability is unclear. To understand whether RvD1 counteracts the lipopolysaccharide (LPS) induced increase in vascular cell permeability, we investigated the effects of RvD1 on endothelial barrier permeability and tight junction reorganization and expression in the presence or absence of LPS stimulation in cultured Human Vascular Endothelial Cells (HUVECs). Our results showed that RvD1 decreased LPS-induced increased in cellular permeability and inhibited the LPS-induced redistribution of zo-1, occludin, and F-actin in HUVECs. Moreover, RvD1 attenuated the expression of IκBα in LPS-induced HUVECs. The NF-κB inhibitor PDTC enhanced the protective effects of RvD1 on restoration of occludin rather than zo-1 expression in LPS-stimulated HUVECs. By contrast, the ERK1/2 inhibitor PD98059 had no effect on LPS-induced alterations in zo-1 and occludin protein expressions in HUVECs. Our data indicate that RvD1 protects against impairment of endothelial barrier function induced by LPS through upregulating the expression of TJ proteins in HUVECs, which involves the IκBα pathway but not the ERK1/2 signaling.

Highlights

Endothelial cells form a selective barrier that dynamically controls the transport of bioactive molecules between the circulating blood and the interstitial fluid [1, 2]
The formation of stress fibers and the changes in tight junctions induced by LPS correlated with a decrease in endothelial barrier function, as measured by passage of Fluorescein isothiocyanate (FITC)-dextran through Human Vascular Endothelial Cells (HUVECs) monolayers grown on Transwell filters
Our results demonstrated that LPS induced an increase in endothelial cell permeability, which was in agreement with previous reports showing that LPS disrupts the permeability barrier of HUVECs [16]

Summary

Introduction

Endothelial cells form a selective barrier that dynamically controls the transport of bioactive molecules between the circulating blood and the interstitial fluid [1, 2] The disruption of this barrier induces a direct increase in vascular permeability. It has been shown that zo-1 limits solute transport, Oxidative Medicine and Cellular Longevity by depleting zo-1 in MDCK cells [5] These investigations suggest that TJ proteins occludin and zo-1 play active roles in regulating paracellular permeability of endothelia [8]. In the present study, we tested the hypothesis that RvD1 could counteract the LPS-induced increase in permeability, primarily through reversing LPS-induced TJ proteins disruption and expression in human umbilical vein endothelial cells (HUVECs)

Materials and Methods

Results

Discussion