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Altered adhesive properties of cord blood endothelial outgrowth cells expressing IL‐1ra
Author(s) -
Fischer Philipp,
Rümmler Marc,
Schulz Christian,
Peschel Christian,
Ott Ilka,
Oostendorp Robert A J
Publication year - 2010
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.2009.106
Subject(s) - proinflammatory cytokine , tumor necrosis factor alpha , microbiology and biotechnology , biology , downregulation and upregulation , cytokine , monocyte , transgene , inflammation , immunology , cancer research , biochemistry , gene
The aim of this study was to examine the potential of endothelial outgrowth cells (EOCs) expanded from CD34 + cord blood‐derived cells (CB‐EOCs) for overexpression of therapeutic transgenes. As proof of principle, we overexpressed icIL‐1ra in CB‐EOCs. Proinflammatory activation of CB‐EOCs in response to cytokine stimulation (IL‐1β and tumor necrosis factor (TNF)) and during coculture with monocytes showed that icIL‐1ra‐expressing CB‐EOCs express significantly reduced levels of ICAM‐1, MCP‐1 and thrombin receptor expression. Moreover, overexpression of icIL‐1ra attenuated the IL‐1β‐mediated proinflammatory activation by diminishing the expression of ICAM‐1, SELE, MCP‐1 and IL‐1β. Interestingly, overexpression of icIL‐1ra also inhibited TNF‐induced upregulation of ICAM‐1. Expression of ICAM‐1, VCAM‐1, tissue factor and IL‐1β was also decreased on direct contact with monocytes. These changes in gene expression were accompanied by functional reduction in leukocyte rolling, adhesion of monocytes to CB‐EOCs, as well as by a reduction in transendothelial migration of monocytes. Our findings show that CB‐EOCs stably expressing transgenic icIL‐1ra are protected against activation by not only IL‐1β but also TNFα‐mediated proinflammatory stimuli and inhibit decisive pathomechanisms of inflammatory processes such as rolling, adhesion and transmigration of monocytes. Therefore, icIL‐ra transgenic CB‐EOCs may prove to be beneficial in the treatment of IL‐1β‐ and TNFα‐mediated inflammatory vasculopathies.