1. Lipopolysaccharide downregulates CD91/low-density lipoprotein receptor-related protein 1 expression through SREBP-1 overexpression in human macrophages
- Author
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V. Llorente-Cortés, Elena Revuelta-López, O. Llampayas, Roi Cal, Rosa Aledo, Lina Badimon, Laura Nasarre, José M. Castellano, Paula Costales, and Cándido Juárez
- Subjects
Lipopolysaccharides ,SREBP-2 ,endocrine system ,LRP1 ,Down-Regulation ,Lipopolysaccharide ,Biology ,digestive system ,Downregulation and upregulation ,polycyclic compounds ,Humans ,Gene silencing ,RNA, Messenger ,Nuclear protein ,Receptor ,Aggregated LDL ,SREBP-1 ,Macrophages ,Nuclear Proteins ,food and beverages ,Cell biology ,Sterol regulatory element-binding protein ,LDLR ,Biochemistry ,LDL receptor ,lipids (amino acids, peptides, and proteins) ,Sterol Regulatory Element Binding Protein 1 ,Cardiology and Cardiovascular Medicine ,Human macrophages ,Low Density Lipoprotein Receptor-Related Protein-1 ,Sterol Regulatory Element Binding Protein 2 ,Lipoprotein - Abstract
Sterol regulatory element-binding proteins (SREBPs) negatively modulate the expression of the CD91/low-density lipoprotein receptor-related protein (LRP1), a carrier and signaling receptor that mediates the endocytosis of more than 40 structurally and functionally distinct ligands. The aim of this work was to analyze whether lipopolysaccharide (LPS) can regulate LRP1 expression through SREBPs in human monocyte-derived macrophages (HMDM). LPS led to LRP1 mRNA and protein inhibition in a dose-and time-dependent manner. Concomitantly, a strong upregulation of SREBP-1 mRNA and SREBP-1 nuclear protein levels was observed in LPS-treated HMDM. The specific silencing of SREBP-1 efficiently prevented LRP1 reduction caused by LPS. SREBP-1 mRNA and nuclear protein levels remained high in HMDM treated with LPS unexposed or exposed to LDL. Native (nLDL) or aggregated LDL (agLDL) per se downregulated SREBP-2 expression levels and increased LRP1 expression. However, lipoproteins did not significantly alter the effect of LPS on SREBP-1 and LRP1 expression. Collectively, these data support that lipoproteins and LPS exert their modulatory effect on LRP1 expression through different SREBP isoforms, SREBP-2 and SREBP-1, respectively. These results highlight a crucial role of SREBP1 as a mediator of the downregulatory effects of LPS on LRP1 expression in human macrophages, independently of the absence or presence of modified lipoproteins. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
- Published
- 2013