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Inflammation Research

Erschienen in:

01.03.2016 | Original Research Paper

Urinary trypsin inhibitor attenuates LPS-induced endothelial barrier dysfunction by upregulation of vascular endothelial-cadherin expression

verfasst von: Jie Chen, Jun Wang, Chenglei Su, Wenyi Qian, Li Sun, Hao Sun, Junjie Chen, Huazhong Zhang, Jinsong Zhang

Erschienen in: Inflammation Research | Ausgabe 3/2016

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Abstract

Introduction

Urinary trypsin inhibitor (UTI) decreases inflammatory cytokine levels and mortality in experimental animal models of inflammation. Here, we observed the effect of UTI on lipopolysaccharide (LPS)-induced hyperpermeability in human umbilical vein endothelial cells (HUVECs) and explored the role of vascular endothelial-cadherin (VE-cadherin) in its effect.

Methods

The effect of UTI on endothelial barrier hyperpermeability was detected by an electrical cell–substrate impedance sensing (ECIS) system and a transwell chamber system. The expression of VE-cadherin in HUVECs was examined by real-time PCR and western blot.

Results

We demonstrated that the alleviation of LPS-induced barrier dysfunction could be achieved by pretreatment with 3000 U/mL of UTI. VE-cadherin monoclonal antibody (mAb) could inhibit the protective effects. UTI maintained VE-cadherin expression by increasing protein stability at both the transcriptional and post-transcriptional levels. Meanwhile, VE-cadherin expression on the cell surface increased when the cells were pretreated with UTI. Furthermore, pretreatment with UTI decreased the phosphorylation of VE-cadherin at Tyr658 but not Tyr731.

Conclusions

Our data show that prophylactic UTI maintains the endothelial barrier function, increases VE-cadherin expression, and inhibits the phosphorylation of VE-cadherin at Tyr658 under inflammatory conditions. It suggests a scientific and potential clinical therapeutic importance of UTI in treatment of inflammatory disorders.

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Titel: Urinary trypsin inhibitor attenuates LPS-induced endothelial barrier dysfunction by upregulation of vascular endothelial-cadherin expression
verfasst von: Jie Chen
Jun Wang
Chenglei Su
Wenyi Qian
Li Sun
Hao Sun
Junjie Chen
Huazhong Zhang
Jinsong Zhang
Publikationsdatum: 01.03.2016
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 3/2016
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-015-0907-9

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Abstract

Introduction

Methods

Results

Conclusions

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