Urinary trypsin inhibitor attenuates LPS-induced endothelial barrier dysfunction by upregulation of vascular endothelial-cadherin expression.
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.
['Chen|Jie|J|', 'Wang|Jun|J|', 'Su|Chenglei|C|', 'Qian|Wenyi|W|', 'Sun|Li|L|', 'Sun|Hao|H|', 'Chen|Junjie|J|', 'Zhang|Huazhong|H|', 'Zhang|Jinsong|J|']
D015703:Antigens, CD D015820:Cadherins D015815:Cell Adhesion Molecules D002463:Cell Membrane Permeability D002465:Cell Movement D002470:Cell Survival D002478:Cells, Cultured D057167:Claudins D006023:Glycoproteins D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D008070:Lipopolysaccharides D008264:Macrophages D012333:RNA, Messenger D011956:Receptors, Cell Surface D015854:Up-Regulation
Urinary trypsin inhibitor Endothelial barrier dysfunction Vascular endothelial-cadherin Lipopolysaccharide