| The activation of liver X receptors inhibits toll-like receptor-9-induced foam cell formation. | |
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MedLine Citation:
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PMID: 20049870 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Toll-like receptors (TLRs) are related to foam cell formation (FCF), key event in the establishment/progression of atherosclerosis. The activation of TLR2 and TLR4 can increase FCF. The aim of this study was to evaluate the role of TLR9 in FCF. Murine macrophages were treated with CpG-ODN, TLR9 agonist, and oxidized particles of LDL (Paz-PC) and FCF was analyzed by means of Oil Red O staining. The administration of CpG-ODN plus Paz-PC onto macrophages increased the amount of lipid droplets, correlated to increased levels of tumor necrosis factor (TNF)-alpha, IFNbeta, and IP-10. The underlying mechanism by which TLR9 ligation influenced Paz-PC in the FCF was NF-kappaB- and IRF7-dependent, as observed by higher levels of phosphorylated IkappaBalpha, increased nuclear translocation of the p65 subunit, lower levels of the total IKKalpha protein and higher release of interferon-dependent cytokines, such as IP-10. Liver X receptors (LXRs) regulate lipid cellular transport and negatively modulate TLR-dependent signaling pathways. Indeed, the addition of GW3965, synthetic LXRs agonist, significantly reduced FCF after CpG-ODN plus Paz-PC stimulation. In this condition, we observed decreased levels of the nuclear translocation of the p65 subunit, related to the higher presence of LXRalpha into the nucleus. TNF-alpha, IP-10, and IFNbeta levels were reduced by the administration of GW3965 following CpG-ODN and Paz-PC treatment. In conclusion, the activation of TLR9 facilitates the formation of foam cells in an NF-kappaB- and IRF7-dependent manner, countered by the activation of LXRs. This study further support LXRs as potential anti-atherosclerotic target. |
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Authors:
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Rosalinda Sorrentino; Silvana Morello; Shuang Chen; Eduardo Bonavita; Aldo Pinto |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular physiology Volume: 223 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-02-01 Completed Date: 2010-03-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 158-67 Citation Subset: IM |
Copyright Information:
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J. Cell. Physiol. 223: 158-167, 2010. (c) 2009 Wiley-Liss, Inc. |
Affiliation:
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Pharmaceutical Science Department, University of Salerno, 84084 Fisciano, Salerno, Italy. rosalinda.sorrentino@googlemail.com |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Azo Compounds Benzoic Acids / pharmacology Benzylamines / pharmacology Cells, Cultured Chemokine CXCL10 / metabolism Coloring Agents Foam Cells / drug effects, metabolism* I-kappa B Proteins / metabolism Inflammation Mediators / metabolism Interferon Regulatory Factor-7 / metabolism Interferon-beta / metabolism Lipid Metabolism* / drug effects Lipoproteins, LDL / pharmacology Macrophages, Peritoneal / drug effects, metabolism* Mice Mice, Inbred C57BL NF-kappa B / metabolism Oligodeoxyribonucleotides / pharmacology Orphan Nuclear Receptors / agonists, metabolism* Phosphorylation Phosphorylcholine / analogs & derivatives, pharmacology Signal Transduction Staining and Labeling / methods Time Factors Toll-Like Receptor 9 / agonists, metabolism* Tumor Necrosis Factor-alpha / metabolism |
| Chemical | |
Reg. No./Substance:
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0/1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine; 0/Azo Compounds; 0/Benzoic Acids; 0/Benzylamines; 0/CPG-oligonucleotide; 0/Chemokine CXCL10; 0/Coloring Agents; 0/GW 3965; 0/I-kappa B Proteins; 0/Inflammation Mediators; 0/Interferon Regulatory Factor-7; 0/Irf7 protein, mouse; 0/Lipoproteins, LDL; 0/NF-kappa B; 0/Oligodeoxyribonucleotides; 0/Orphan Nuclear Receptors; 0/Tlr9 protein, mouse; 0/Toll-Like Receptor 9; 0/Tumor Necrosis Factor-alpha; 0/liver X receptor; 0/oxidized low density lipoprotein; 107-73-3/Phosphorylcholine; 1320-06-5/oil red O; 139874-52-5/NF-kappaB inhibitor alpha; 77238-31-4/Interferon-beta |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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