| High-density lipoprotein suppresses the type I interferon response, a family of potent antiviral immunoregulators, in macrophages challenged with lipopolysaccharide. | |
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MedLine Citation:
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PMID: 20974999 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: High-density lipoprotein (HDL) protects the artery wall by removing cholesterol from lipid-laden macrophages. However, recent evidence suggests that HDL might also inhibit atherogenesis by combating inflammation. METHODS AND RESULTS: To identify potential antiinflammatory mechanisms, we challenged macrophages with lipopolysaccharide, an inflammatory microbial ligand for Toll-like receptor 4. HDL inhibited the expression of 30 (277 of 911) of the genes normally induced by lipopolysaccharide, microarray analysis revealed. One of its major targets was the type I interferon response pathway, a family of potent viral immunoregulators controlled by Toll-like receptor 4 and the TRAM/TRIF signaling pathway. Unexpectedly, the ability of HDL to inhibit gene expression was independent of macrophage cholesterol stores. Immunofluorescent studies suggested that HDL promoted TRAM translocation to intracellular compartments, which impaired subsequent signaling by Toll-like receptor 4 and TRIF. To examine the potential in vivo relevance of the pathway, we used mice deficient in apolipoprotein A-I, the major protein of HDL. After infection with Salmonella typhimurium, a Gram-negative bacterium that expresses lipopolysaccharide, apolipoprotein A-I-deficient mice had 6-fold higher plasma levels of interferon-β, a key regulator of the type I interferon response, than did wild-type mice. CONCLUSIONS: HDL inhibits a subset of lipopolysaccharide-stimulated macrophage genes that regulate the type I interferon response, and its action is independent of sterol metabolism. These findings raise the possibility that regulation of macrophage genes by HDL might link innate immunity and cardioprotection. |
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Authors:
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Masashi Suzuki; David K Pritchard; Lev Becker; Andrew N Hoofnagle; Natsuko Tanimura; Theo K Bammler; Richard P Beyer; Roger Bumgarner; Tomas Vaisar; Maria C de Beer; Frederick C de Beer; Kensuke Miyake; John F Oram; Jay W Heinecke |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-10-25 |
Journal Detail:
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Title: Circulation Volume: 122 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-09 Completed Date: 2010-12-23 Revised Date: 2013-05-27 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 1919-27 Citation Subset: AIM; IM |
Affiliation:
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Department of Medicine, University of Washington, Seattle, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Chemokine CXCL10 / secretion Chemokines / genetics Cytokines / genetics Gene Expression Regulation / drug effects, physiology Immunosuppression Interferon Type I / immunology* Interferon-beta / secretion Interleukin-12 / secretion Lipopolysaccharides / pharmacology* Lipoproteins, HDL / pharmacology* Macrophages / drug effects, immunology* Mice Mice, Inbred C57BL RNA, Messenger / genetics Signal Transduction / physiology Thioglycolates / pharmacology Toll-Like Receptor 4 / agonists, genetics Toll-Like Receptors / genetics |
| Grant Support | |
ID/Acronym/Agency:
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DK017047/DK/NIDDK NIH HHS; HL030086/HL/NHLBI NIH HHS; HL072370/HL/NHLBI NIH HHS; HL085437/HL/NHLBI NIH HHS; HL086670/HL/NHLBI NIH HHS; HL086798/HL/NHLBI NIH HHS; HL092969/HL/NHLBI NIH HHS; P01 HL030086-25/HL/NHLBI NIH HHS; P01 HL092969-51/HL/NHLBI NIH HHS; P01HL018645/HL/NHLBI NIH HHS; P01HL030086/HL/NHLBI NIH HHS; P30DK017047/DK/NIDDK NIH HHS; P30ES07033/ES/NIEHS NIH HHS; R01 AG010886-05/AG/NIA NIH HHS; R01 HL085437-05/HL/NHLBI NIH HHS; R01 HL086798-05/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CXCL10; 0/Chemokines; 0/Cytokines; 0/Interferon Type I; 0/Lipopolysaccharides; 0/Lipoproteins, HDL; 0/RNA, Messenger; 0/Thioglycolates; 0/Tlr4 protein, mouse; 0/Toll-Like Receptor 4; 0/Toll-Like Receptors; 187348-17-0/Interleukin-12; 77238-31-4/Interferon-beta |
| Comments/Corrections | |
Comment In:
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Circulation. 2010 Nov 9;122(19):1900-1
[PMID:
20974995
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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