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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2003-10-28
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pubmed:abstractText |
The liver X receptors (LXR) alpha and beta are regulators of cholesterol metabolism and determinants of atherosclerosis susceptibility. Viral and bacterial pathogens have long been suspected to be modulators of atherogenesis; however, mechanisms linking innate immunity to cholesterol metabolism are poorly defined. We demonstrate here that pathogens interfere with macrophage cholesterol metabolism through inhibition of the LXR signaling pathway. Activation of Toll-like receptors (TLR) 3 and 4 by microbial ligands blocks the induction of LXR target genes including ABCA1 in cultured macrophages as well as in aortic tissue in vivo. As a consequence of these transcriptional effects, TLR3/4 ligands strongly inhibit cholesterol efflux from macrophages. Crosstalk between LXR and TLR signaling is mediated by IRF3, a specific effector of TLR3/4 that inhibits the transcriptional activity of LXR on its target promoters. These findings highlight a common mechanism whereby bacterial and viral pathogens may modulate macrophage cholesterol metabolism and cardiovascular disease.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP binding cassette transporter 1,
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon Regulatory Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/Irf3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myd88 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloid Differentiation Factor 88,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Orphan Nuclear Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 3,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/liver X receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1097-2765
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
805-16
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:14580333-ATP-Binding Cassette Transporters,
pubmed-meshheading:14580333-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:14580333-Animals,
pubmed-meshheading:14580333-Antigens, Differentiation,
pubmed-meshheading:14580333-Arteriosclerosis,
pubmed-meshheading:14580333-Bacterial Infections,
pubmed-meshheading:14580333-Cell Line,
pubmed-meshheading:14580333-Cholesterol,
pubmed-meshheading:14580333-DNA-Binding Proteins,
pubmed-meshheading:14580333-Gene Expression Regulation,
pubmed-meshheading:14580333-Genes, Regulator,
pubmed-meshheading:14580333-Interferon Regulatory Factor-3,
pubmed-meshheading:14580333-Ligands,
pubmed-meshheading:14580333-Macrophages,
pubmed-meshheading:14580333-Membrane Glycoproteins,
pubmed-meshheading:14580333-Mice,
pubmed-meshheading:14580333-Mice, Inbred C57BL,
pubmed-meshheading:14580333-Mice, Knockout,
pubmed-meshheading:14580333-Myeloid Differentiation Factor 88,
pubmed-meshheading:14580333-NF-kappa B,
pubmed-meshheading:14580333-Orphan Nuclear Receptors,
pubmed-meshheading:14580333-Promoter Regions, Genetic,
pubmed-meshheading:14580333-Receptors, Cell Surface,
pubmed-meshheading:14580333-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:14580333-Receptors, Immunologic,
pubmed-meshheading:14580333-Signal Transduction,
pubmed-meshheading:14580333-Toll-Like Receptor 3,
pubmed-meshheading:14580333-Toll-Like Receptors,
pubmed-meshheading:14580333-Transcription Factors,
pubmed-meshheading:14580333-Virus Diseases
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pubmed:year |
2003
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pubmed:articleTitle |
Crosstalk between LXR and toll-like receptor signaling mediates bacterial and viral antagonism of cholesterol metabolism.
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pubmed:affiliation |
Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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