IL-11 protects human microvascular endothelium from alloinjury in vivo by induction of survivin expression |
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Authors: | Kirkiles-Smith Nancy C Mahboubi Keyvan Plescia Janet McNiff Jennifer M Karras James Schechner Jeffrey S Altieri Dario C Pober Jordan S |
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Institution: | Interdepartmental Program in Vascular Biology and Transplantation, Boyer Center for Molecular Medicine and Department of Pathology, Yale University School of Medicine, New Haven CT 06510, USA. |
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Abstract: | IL-11 can reduce tissue injury in animal models of inflammation but the mechanism(s) is unknown. When C.B-17 SCID/beige mice bearing human skin grafts are injected i.p. with human PBMC allogeneic to the donor skin, infiltrating T cells destroy human microvessels by day 21. Intradermal injection of human IL-11 (500 ng/day) delays the time course of graft microvessel loss without reducing the extent of T cell infiltration. Protective actions of IL-11 are most pronounced on day 15. IL-11 has no effect on T cell activation marker, effector molecule, cytokine expression, or endothelial ICAM-1 expression. IL-11 up-regulates the expression of survivin, a cytoprotective protein, in graft keratinocytes and endothelial cells. Topical application of survivin antisense oligonucleotide down-regulates survivin expression in both cell types and largely abrogates the protective effect of IL-11. We conclude that in this human transplant model, IL-11 exerts a cytoprotective rather than anti-inflammatory or immunomodulatory effect mediated through induction of survivin. |
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