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Pou, Jordi; Martínez-González, José; Rebollo, Alba; Rodríguez, Cristina; Rodríguez-Calvo, Ricardo; Martín-Fuentes, Paula; Cenarro, Ana; Civeira, Fernando; Laguna, Juan C.; Alegret, Marta
Biochimica et biophysica acta, 09/2011, Letnik: 1811, Številka: 9Journal Article
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. ► IL-1R2 expression is lower in monocytes from patients with FCH. ► Acetylated LDL and VLDL reduce IL-1R2 expression in THP-1 macrophages. ► These lipoproteins prevent the increase in IL-1R2 expression induced by LPS. ► IL-1R2 protein expression is lower in atherosclerotic vs. normal human vessels. ► Reduced IL-1R2 expression could facilitate IL-1 signaling.
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