Document Detail


High-density lipoprotein suppresses the type I interferon response, a family of potent antiviral immunoregulators, in macrophages challenged with lipopolysaccharide.
MedLine Citation:
PMID:  20974999     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
12507889 - Regulation of macrophage migration inhibitory factor expression by glucocorticoids in v...
9107159 - Oxidized low-density lipoprotein induces apoptosis of human endothelial cells by activa...
20198449 - Activation of cd74 inhibits migration of human mesenchymal stem cells.
25034969 - Mechanism of hbγ-35-induced an increase in the activation of the human immune system b...
19942609 - Oxidized low-density lipoproteins upregulate proline oxidase to initiate ros-dependent ...
17373669 - Macrophage migration inhibitory factor is essential for allergic asthma but not for th2...
11240649 - Cytokines il-1beta, il-2, il-6, il-8, mcp-1, gm-csf and tnfalpha in patients with epith...
16154209 - Induction of suppressors of cytokine signaling (socs) in the retina during experimental...
21525629 - Cellular effects of catabolic inflammatory cytokines on chondrocytes - biomed 2011.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-10-25
Journal Detail:
Title:  Circulation     Volume:  122     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-09     Completed Date:  2010-12-23     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1919-27     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, University of Washington, Seattle, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
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:
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:
Circulation. 2010 Nov 9;122(19):1900-1   [PMID:  20974995 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Effects of HIV protease inhibitors on progression of monocrotaline- and hypoxia-induced pulmonary hy...
Next Document:  Relationship of echocardiographic dyssynchrony to long-term survival after cardiac resynchronization...