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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0021469,
umls-concept:C0037083,
umls-concept:C0185117,
umls-concept:C0205548,
umls-concept:C0805732,
umls-concept:C1150611,
umls-concept:C1335960,
umls-concept:C1366753,
umls-concept:C1412058,
umls-concept:C1548425,
umls-concept:C1710082,
umls-concept:C2911684
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pubmed:issue |
2
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pubmed:dateCreated |
2009-3-30
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pubmed:abstractText |
Interferon gamma (IFN-gamma) is an immunomodulatory and anti-microbial cytokine, which has a variety of proatherogenic effects. It has been reported that IFN-gamma can down-regulate ABCA1 expression. However, its mechanism is elusive. In the present study, we have investigated the effect of IFN-gamma on ABCA1 expression and cholesterol efflux in THP-1 macrophage-derived foam cells. IFN-gamma decreased ABCA1 expression at both transcriptional and translational levels in a dose-dependent manner. Cellular cholesterol content was increased while cholesterol efflux was decreased by IFN-gamma treatment. Liver X receptor alpha (LXRalpha), which can regulate the expression of ABCA1, was also down-regulated by IFN-gamma treatment. LXRalpha-specific activation by LXRalpha agonist almost compensated the down-regulation of ABCA1 expression by IFN-gamma, while siRNA of LXRalpha led to down-regulation of ABCA1 expression more significantly than IFN-gamma. IFN-gamma induced phosphorylation of STAT1 and expression of STAT1alpha in the nucleus, which was inhibited by a JAK inhibitor AG-490. Treatment with STAT1 siRNA further enhanced down-regulation of LXRalpha mRNA by IFN-gamma. Furthermore, AG-490 and STAT1 siRNA almost compensated the effect of IFN-gamma on ABCA1 expression and cholesterol efflux. In conclusion, IFN-gamma may first down-regulate expression of LXRalpha through the JAK/STAT1 signaling pathway and then decrease expression of ABCA1 and cholesterol efflux in THP-1 macrophage-derived foam cells. Therefore, our study may be useful in understanding the critical effect of IFN-gamma in pathogenesis of atherosclerosis.
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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/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Orphan Nuclear Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/STAT1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-cyano-(3,4-dihydroxy)-N-benzyl...,
http://linkedlifedata.com/resource/pubmed/chemical/liver X receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1879-1484
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
203
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
417-28
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18789440-ATP-Binding Cassette Transporters,
pubmed-meshheading:18789440-Atherosclerosis,
pubmed-meshheading:18789440-Cholesterol,
pubmed-meshheading:18789440-DNA-Binding Proteins,
pubmed-meshheading:18789440-Dose-Response Relationship, Drug,
pubmed-meshheading:18789440-Down-Regulation,
pubmed-meshheading:18789440-Gene Expression Regulation,
pubmed-meshheading:18789440-Humans,
pubmed-meshheading:18789440-Interferon-gamma,
pubmed-meshheading:18789440-Janus Kinase 1,
pubmed-meshheading:18789440-Macrophages,
pubmed-meshheading:18789440-Orphan Nuclear Receptors,
pubmed-meshheading:18789440-Phosphorylation,
pubmed-meshheading:18789440-RNA, Small Interfering,
pubmed-meshheading:18789440-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:18789440-STAT1 Transcription Factor,
pubmed-meshheading:18789440-Signal Transduction,
pubmed-meshheading:18789440-Tyrphostins
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pubmed:year |
2009
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pubmed:articleTitle |
IFN-gamma down-regulates ABCA1 expression by inhibiting LXRalpha in a JAK/STAT signaling pathway-dependent manner.
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pubmed:affiliation |
Institute of Cardiovascular Research, Life Science Research Center, University of South China, Nanhua University, Hengyang, Hunan, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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