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Browsing by Author "Goldish, Danny"

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    IL-4 Induces Protection of Porcine Endothelial Cells from Anti-Endothelial Cell Antibody in Association with Upregulation of Claudin-5
    (2010-04-21) Goldish, Danny
    Interspecies organ transplantation offers a potential strategy to the global shortage in vital human organs for donation. Multiple obstacles remain before rejection of foreign organ grafts (xenotransplantation) can be avoided. In pig-to-primate combinations, the vascular endothelium of the transplant is the main target of injury by the host immune system. We are using an in vitro system in which pig endothelial cells (EC) are modified to make them resistant to injury by anti-EC antibodies (abs) in human blood. These abs damage the EC by causing cellular retraction and intercellular gap formation. My aim is to study methods and mechanisms that protect the EC from injury caused by the abs. The cytokine interleukin-4 (IL-4) induces protection of EC from apoptosis and from killing by human complement. My results demonstrated that pretreatment of the EC with pig IL-4 decreases the amount of abinduced cellular retraction and intercellular gap formation. This finding suggested that IL-4 might regulate the expression of proteins that maintain cell-to-cell junctions in the monolayer. Using immunofluoresce, we examined the expression of the junction proteins CD31, VEcadherin, and claudin-5, in IL-4-treated and untreated EC. We found that IL-4 strongly induces claudin-5 expression, but not expression of VE-cadherin or CD31. We now plan to use siRNA silencing of claudin-5 to investigate whether increases in claudin-5 protein are important for protection of EC from ab-induced damage. If this silencing abolishes EC protection, claudin-5 must play a pivotal role in IL-4-induced protection. Conversely, if protection still occurs, claudin-5 is an unnecessary side reaction of the protection. This information will help uncover mechanisms behind IL-4 induced protection, and contribute to new approaches for xenotransplantation.