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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2005-2-3
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pubmed:abstractText |
Interleukin (IL)-10 may have a therapeutic potential in atherosclerosis, but its mechanisms of action have not been clarified. Foam cell formation is a key event in atherogenesis, and apoptosis of these lipid-laden cells may promote plaque destabilization. We sought to explore whether IL-10 could have plaque-stabilizing properties in acute coronary syndromes (ACS). We studied the effect of IL-10 on oxidized low density lipoprotein (oxLDL)-stimulated THP-1 cells and monocyte-derived macrophages from ACS patients and healthy controls using different experimental approaches. Our main findings were: i) IL-10 enhances lipid accumulation in oxLDL-stimulated THP-1 macrophages, at least partly by counteracting oxLDL-induced apoptosis; ii) This antiapoptotic effect of IL-10 involves increased expression of the antiapoptotic genes Bfl-1 and Mcl-1, accompanied by protective effects on mitochondria function; iii) By silencing Bfl-1 and Mcl-1 genes using siRNAs, we were able to abolish this IL-10-mediated effect on lipid accumulation; iv) IL-10 also induced lipid accumulation in oxLDL-stimulated macrophages from patients with ACS, but not in macrophages from healthy controls; v) In ACS patients, this enhancing effect of IL-10 on lipid accumulation was accompanied by enhanced Mcl-1 expression. No such antiapoptotic effect was seen in macrophages from healthy controls. These findings suggest a new mechanism for the effect of IL-10 in atherosclerosis, possibly contributing to plaque stabilization.
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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/Azo Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/BCL2-related protein A1,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-10,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/myeloid cell leukemia sequence 1...,
http://linkedlifedata.com/resource/pubmed/chemical/oil red O,
http://linkedlifedata.com/resource/pubmed/chemical/oxidized low density lipoprotein
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-2275
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pubmed:author |
pubmed-author:AukrustPålP,
pubmed-author:BiessenErik AEA,
pubmed-author:DamåsJan KristianJK,
pubmed-author:FrølandStig SSS,
pubmed-author:HallChristianC,
pubmed-author:HalvorsenBenteB,
pubmed-author:HavauxBB,
pubmed-author:HeimliHildeH,
pubmed-author:MüllerFredrikF,
pubmed-author:ScholzHanneH,
pubmed-author:TonstadSerenaS,
pubmed-author:WaehreTorgunT,
pubmed-author:von der ThüsenJan HJH
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pubmed:issnType |
Print
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pubmed:volume |
46
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
211-9
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pubmed:dateRevised |
2008-7-9
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pubmed:meshHeading |
pubmed-meshheading:15547296-Apoptosis,
pubmed-meshheading:15547296-Arteriosclerosis,
pubmed-meshheading:15547296-Azo Compounds,
pubmed-meshheading:15547296-Case-Control Studies,
pubmed-meshheading:15547296-Cells, Cultured,
pubmed-meshheading:15547296-Dose-Response Relationship, Drug,
pubmed-meshheading:15547296-Foam Cells,
pubmed-meshheading:15547296-Humans,
pubmed-meshheading:15547296-Interleukin-10,
pubmed-meshheading:15547296-Leukocytes, Mononuclear,
pubmed-meshheading:15547296-Lipid Metabolism,
pubmed-meshheading:15547296-Lipoproteins, LDL,
pubmed-meshheading:15547296-Macrophages,
pubmed-meshheading:15547296-Mitochondria,
pubmed-meshheading:15547296-Monocytes,
pubmed-meshheading:15547296-Neoplasm Proteins,
pubmed-meshheading:15547296-Oxygen,
pubmed-meshheading:15547296-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:15547296-RNA, Messenger,
pubmed-meshheading:15547296-RNA, Small Interfering,
pubmed-meshheading:15547296-Time Factors,
pubmed-meshheading:15547296-Transfection
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pubmed:year |
2005
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pubmed:articleTitle |
Interleukin-10 enhances the oxidized LDL-induced foam cell formation of macrophages by antiapoptotic mechanisms.
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pubmed:affiliation |
Research Institute for Internal Medicine, The National Hospital, Oslo, Norway. bente.halvorsen@klinmed.uio.no
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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