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• W1997472009 abstract "Objectives Interleukin (IL)-1 produced by vascular and bone marrow-derived cells exerts proinflammatory effects in these cell types by binding to IL-1 receptor type-1 (IL-1R1). We have previously shown that bone marrow-derived IL-1α and IL-1β are critical for atherogenesis in apoE knockout (KO) mice. The aim of the present study was to investigate whether IL-1R1 on vascular wall resident or bone marrow-derived cells mediates IL-1's effects in atherogenesis. Methods and results We generated apoE−/−/IL-1R1−/− double knockout (DKO) mice and created radiation chimeras. Aortic sinus lesion area was 20–47% lower in DKO compared to apoE KO mice with similar plasma lipids. The production of IL-1α and IL-1β upon stimulation with LPS was not altered in IL-1R1−/− compared to IL-1R1+/+ peritoneal macrophages. DKO mice transplanted with IL-1R1+/+ bone marrow-derived cells had reduced (48%) aortic sinus lesion compared to apoE KO mice while specific deficiency of IL-1R1 in bone marrow-derived cells did not attenuate atherosclerosis. The mRNA levels of genes that promote macrophage recruitment to the vascular wall, namely CD68, VCAM-1, ICAM-1 and MCP-1 were lower in aortas from DKO compared to apoE KO mice. Finally, blockade of IL-1R1 with IL-1R antagonist (IL-1Ra) resulted in complete abrogation of IL-1β-induced expression of adhesion and chemotactic molecules and IL-1α, in isolated human umbilical vein endothelial cells (HUVEC). Conclusions Vascular wall resident cells are the main targets for the pro-atherogenic effects of bone marrow-derived IL-1 through IL-1R1, partly by induction of adhesion and chemotactic molecules in endothelial cells." @default.
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• W1997472009 date "2012-06-01" @default.
• W1997472009 modified "2023-09-26" @default.
• W1997472009 title "Interleukin-1 receptor type-1 in non-hematopoietic cells is the target for the pro-atherogenic effects of interleukin-1 in apoE-deficient mice" @default.
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• W1997472009 doi "https://doi.org/10.1016/j.atherosclerosis.2011.12.010" @default.
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