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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Antigens, CD, Cadherins, Cell Adhesion Molecules, Cell Membrane Permeability, Cell Movement, Cell Survival, Cells, Cultured, Claudins, Glycoproteins, Human Umbilical Vein Endothelial Cells, Humans, Lipopolysaccharides, Macrophages, RNA, Messenger, Receptors, Cell Surface, Up-Regulation.
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Does urinary trypsin inhibitor attenuate LPS-induced endothelial barrier dysfunction by upregulation of vascular endothelial-cadherin expression? Context: 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. 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. 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.
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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. Final Decision: yes