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Anupriya, M.G. and Sneha, Singh and Neha Vijay , Hulyalkara and E , Sreekumara (2018) Sphingolipid signaling modulates trans-endothelial cell permeability in dengue virus infected HMEC-1 cells. Prostaglandins & other lipid mediators, 136. pp. 44-54. ISSN 1098-8823

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Abstract

Dengue has emerged as a major mosquito-borne disease in the tropics and subtropics. In severe dengue, enhanced microvascular endothelial permeability leads to plasma leakage. Direct dengue virus (DENV) infection in human microvascular endothelial cells (HMEC-1) can enhance trans-endothelial leakage. Using a microarray-based analysis, we identified modulation of key endothelial cell signaling pathways in DENV-infected HMEC-1 cells. One among them was the sphingolipid pathway that regulates vascular barrier function. Sphingosine-1-phosphate receptor 2 (S1PR2) and S1PR5 showed significant up-regulation in the microarray data. In DENV-infected cells, the kinetics of S1PR2 transcript expression and enhanced in vitro trans-endothelial permeability showed a correlation. We also observed an internalization and cytoplasmic translocation of VE-Cadherin, a component of adherens junctions (AJ), upon infection indicating AJ disassembly. Further, inhibition of S1PR2 signaling by a specific pharmacological inhibitor prevented translocation of VE-Cadherin, thus helping AJ maintenance, and abrogated DENV-induced trans-endothelial leakage. Our results show that sphingolipid signaling, especially that involving S1PR2, plays a critical role in vascular leakage in dengue.

Item Type: Article
Uncontrolled Keywords: Endothelium Microarray Dengue DHF Sphingosine kinase JTE-013 FTY720
Subjects: Molecular Virology
Depositing User: Rgcb Library
Date Deposited: 05 Jul 2018 09:52
Last Modified: 11 Apr 2019 11:11
URI: http://rgcb.sciencecentral.in/id/eprint/638

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