title: Type II interleukin-1 receptor expression is reduced in monocytes/macrophages and atherosclerotic lesions.
abstract: Type II interleukin-1 receptor (IL-1R2) is a non-signaling decoy receptor that negatively regulates the activity of interleukin-1 (IL-1), a pro-inflammatory cytokine involved in atherogenesis. In this article we assessed the relevance of IL-1R2 in atherosclerosis by studying its expression in monocytes from hyperlipidemic patients, in THP-1 macrophages exposed to lipoproteins and in human atherosclerotic lesions. Our results showed that the mRNA and protein expression of IL-1R2 was reduced in monocytes from patients with familial combined hyperlipidemia (-30%, p<0.05). THP-1 macrophages incubated with increasing concentrations of acetylated low density (ac-LDL) and very low density (VLDL) lipoproteins also exhibit a decrease in IL-1R2 mRNA and protein levels. Pre-incubation with agents that block intracellular accumulation of lipids prevents the decrease in IL-1R2 mRNA caused by lipoproteins. Lipoproteins also prevented the increase in IL-1R1 and IL-1R2 caused by a 4-h stimulation with LPS and reduced protein expression of total and phosphorylated IL-1 receptor-associated kinase-1. Finally, IL-1R2 expression in human atherosclerotic vessels was markedly lower than in non-atherosclerotic arteries (-80%, p<0.0005). Overall, our results suggest that under atherogenic conditions, there is a decrease in IL-1R2 expression in monocytes/macrophages and in the vascular wall that may facilitate IL-1 signaling.
authors.affiliation: Unidad de Farmacología, Facultad de Farmacia, Instituto de Biomedicina (IBUB), Universidad de Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Pou
authors.forename: José
authors.initials: J
authors.lastname: Martínez-González
authors.forename: Alba
authors.initials: A
authors.lastname: Rebollo
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rodríguez-Calvo
authors.forename: Paula
authors.initials: P
authors.lastname: Martín-Fuentes
authors.forename: Ana
authors.initials: A
authors.lastname: Cenarro
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
authors.forename: Juan C
authors.initials: JC
authors.lastname: Laguna
authors.forename: Marta
authors.initials: M
authors.lastname: Alegret
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D058226:Plaque, Atherosclerotic / Q000378:metabolism*; D053574:Receptors, Interleukin-1 Type II / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: C508592:IL1R2 protein, human; D007375:Interleukin-1; D053574:Receptors, Interleukin-1 Type II