IL-11 protects human microvascular endothelium from alloinjury in vivo by induction of survivin expression

NC Kirkiles-Smith, K Mahboubi, J Plescia… - The Journal of …, 2004 - journals.aai.org
NC Kirkiles-Smith, K Mahboubi, J Plescia, JM McNiff, J Karras, JS Schechner, DC Altieri
The Journal of Immunology, 2004journals.aai.org
IL-11 can reduce tissue injury in animal models of inflammation but the mechanism (s) is
unknown. When CB-17 SCID/beige mice bearing human skin grafts are injected ip 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 …
Abstract
IL-11 can reduce tissue injury in animal models of inflammation but the mechanism (s) is unknown. When CB-17 SCID/beige mice bearing human skin grafts are injected ip 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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