Source:http://linkedlifedata.com/resource/pubmed/id/10845873
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2000-6-22
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pubmed:abstractText |
Cholesterol efflux is a fundamental process that serves to mitigate cholesterol accumulation and macrophage foam cell formation. Recently, we reported that cholesterol efflux to high density lipoprotein subfraction 3 was reduced by interferon-gamma (IFN-gamma) and that this decrease was associated with an increase in acyl coenzyme A:cholesterol acyltransferase (ACAT) expression. In the present study, although treatment of murine peritoneal macrophages with IFN-gamma resulted in a 2-fold decrease in HDL-mediated cholesterol efflux, efflux to lipid-free apolipoprotein A-I was reduced >4-fold and approached basal levels. This decrease was associated with a 3- to 4-fold reduction in ATP-binding-cassette transporter 1 (ABC1) mRNA content, the gene responsible for the defect in Tangier disease. Consistent with the reduction in cholesterol and phospholipid efflux in Tangier fibroblasts, downregulation of ABC1 expression by IFN-gamma also resulted in reduced phosphatidylcholine and sphingomyelin efflux to apolipoprotein A-I. Whereas foam cells had a 3-fold increase in ABC1 mRNA, the decrease in ABC1 message levels by IFN-gamma was observed in foam cells and control macrophages. This effect of IFN-gamma was independent of general macrophage activation (inasmuch as similar changes were not detected with granulocyte-macrophage colony-stimulating factor) and was not observed with other ABC transporters (inasmuch as the expression of the transporter in antigen processing was upregulated 4-fold in these same cells). Therefore, by decreasing cholesterol efflux through pathways that include the upregulation of ACAT and the downregulation of ABC1, IFN-gamma can shift the equilibrium between macrophages and foam cells and thus impact the progression of an atherosclerotic lesion.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATP-Binding Cassette Transporters,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoprotein A-I,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1079-5642
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1565-71
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10845873-ATP-Binding Cassette Transporters,
pubmed-meshheading:10845873-Animals,
pubmed-meshheading:10845873-Apolipoprotein A-I,
pubmed-meshheading:10845873-Cholesterol,
pubmed-meshheading:10845873-Foam Cells,
pubmed-meshheading:10845873-Gene Expression Regulation,
pubmed-meshheading:10845873-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:10845873-Interferon-gamma,
pubmed-meshheading:10845873-Macrophages, Peritoneal,
pubmed-meshheading:10845873-Mice,
pubmed-meshheading:10845873-Mice, Inbred BALB C,
pubmed-meshheading:10845873-Tangier Disease
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pubmed:year |
2000
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pubmed:articleTitle |
Interferon-gamma induces downregulation of Tangier disease gene (ATP-binding-cassette transporter 1) in macrophage-derived foam cells.
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pubmed:affiliation |
Division of Cardiovascular Research, Lilly Research Labs, Indianapolis, IN 46285, USA.
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pubmed:publicationType |
Journal Article
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