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: Jordi Pou, José Martínez-González, Alba Rebollo, Cristina Rodríguez, Ricardo Rodríguez-Calvo, Paula Martín-Fuentes, Ana Cenarro, Fernando Civeira, Juan C Laguna, Marta Alegret
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1811 Issue 9 Pg. 556-63 (Sep 2011) ISSN: 0006-3002 [Print] Netherlands
• PMID: 21683158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• IL1R2 protein, human
• Interleukin-1
• Receptors, Interleukin-1 Type II

Topics

• Atherosclerosis (metabolism, pathology)
• Cell Line
• Humans
• Interleukin-1 (metabolism)
• Macrophages (metabolism)
• Male
• Monocytes (metabolism)
• Plaque, Atherosclerotic (metabolism)
• Receptors, Interleukin-1 Type II (genetics, metabolism)
• Signal Transduction (physiology)