Type II interleukin-1 receptor expression is reduced in monocytes/macrophages and atherosclerotic lesions
Por:
Pou, J, Martinez-Gonzalez, J, Rebollo, A, Rodriguez, C, Rodriguez-Calvo, R, Martin-Fuentes, P, Cenarro, A, Civeira, F, Laguna, JC, Alegret, M
Publicada:
1 sep 2011
Resumen:
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 1L-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. (C) 2011 Elsevier B.V. All rights reserved.
Filiaciones:
Pou, J:
Univ Barcelona, Fac Farm, Unidad Farmacol, Inst Biomed IBUB, E-08028 Barcelona, Spain
Martinez-Gonzalez, J:
IBB St Pau, Ctr Invest Cardiovasc CSIC ICCC, Barcelona, Spain
Rebollo, A:
Univ Barcelona, Fac Farm, Unidad Farmacol, Inst Biomed IBUB, E-08028 Barcelona, Spain
Rodriguez, C:
IBB St Pau, Ctr Invest Cardiovasc CSIC ICCC, Barcelona, Spain
Rodriguez-Calvo, R:
IBB St Pau, Ctr Invest Cardiovasc CSIC ICCC, Barcelona, Spain
Martin-Fuentes, P:
Hosp Univ Miguel Servet, Unidad Lipidos, Inst Argones Ciencias Salud I CS, Zaragoza, Spain
Hosp Univ Miguel Servet, Inst Aragones Ciencias Salud I CS, Lab Invest Mol, Zaragoza, Spain
Cenarro, A:
Hosp Univ Miguel Servet, Unidad Lipidos, Inst Argones Ciencias Salud I CS, Zaragoza, Spain
Hosp Univ Miguel Servet, Inst Aragones Ciencias Salud I CS, Lab Invest Mol, Zaragoza, Spain
Civeira, F:
Hosp Univ Miguel Servet, Unidad Lipidos, Inst Argones Ciencias Salud I CS, Zaragoza, Spain
Hosp Univ Miguel Servet, Inst Aragones Ciencias Salud I CS, Lab Invest Mol, Zaragoza, Spain
Laguna, JC:
Univ Barcelona, Fac Farm, Unidad Farmacol, Inst Biomed IBUB, E-08028 Barcelona, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid, Spain
Alegret, M:
Univ Barcelona, Fac Farm, Unidad Farmacol, Inst Biomed IBUB, E-08028 Barcelona, Spain
Inst Salud Carlos III, CIBER Fisiopatol Obesidad & Nutr, Madrid, Spain
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