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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2010-2-17
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pubmed:abstractText |
The orphan receptor LRH-1 and the oxysterol receptors LXRalpha and LXRbeta are established transcriptional regulators of lipid metabolism that appear to control inflammatory processes. Here, we investigate the anti-inflammatory actions of these nuclear receptors in the hepatic acute phase response (APR). We report that selective synthetic agonists induce SUMOylation-dependent recruitment of either LRH-1 or LXR to hepatic APR promoters and prevent the clearance of the N-CoR corepressor complex upon cytokine stimulation. Investigations of the APR in vivo, using LXR knockout mice, indicate that the anti-inflammatory actions of LXR agonists are triggered selectively by the LXRbeta subtype. We further find that hepatic APR responses in small ubiquitin-like modifier-1 (SUMO-1) knockout mice are increased, which is due in part to diminished LRH-1 action at APR promoters. Finally, we provide evidence that the metabolically important coregulator GPS2 functions as a hitherto unrecognized transrepression mediator of interactions between SUMOylated nuclear receptors and the N-CoR corepressor complex. Our study extends the knowledge of anti-inflammatory mechanisms and pathways directed by metabolic nuclear receptor-corepressor networks to the control of the hepatic APR, and implies alternative pharmacological strategies for the treatment of human metabolic diseases associated with inflammation.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20159957-11090131,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20159957-11238557,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20159957-11931768,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/20159957-9971870
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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/Anti-Inflammatory Agents,
http://linkedlifedata.com/resource/pubmed/chemical/GPS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/NR5A2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Orphan Nuclear Receptors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Small Ubiquitin-Related Modifier...,
http://linkedlifedata.com/resource/pubmed/chemical/liver X receptor
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1549-5477
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pubmed:author |
pubmed-author:DamdimopoulosAnastasiosA,
pubmed-author:EhrlundAnnaA,
pubmed-author:EllisEwaE,
pubmed-author:GustafssonJan-AkeJA,
pubmed-author:JänneOlli AOA,
pubmed-author:JakobssonTomasT,
pubmed-author:MikkonenLauraL,
pubmed-author:NilssonLisa-MariLM,
pubmed-author:PariniPaoloP,
pubmed-author:SteffensenKnut RKR,
pubmed-author:TreuterEckardtE,
pubmed-author:VenteclefNicolasN
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
381-95
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pubmed:dateRevised |
2010-9-28
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pubmed:meshHeading |
pubmed-meshheading:20159957-Acute-Phase Reaction,
pubmed-meshheading:20159957-Animals,
pubmed-meshheading:20159957-Anti-Inflammatory Agents,
pubmed-meshheading:20159957-COS Cells,
pubmed-meshheading:20159957-Cercopithecus aethiops,
pubmed-meshheading:20159957-Female,
pubmed-meshheading:20159957-Gene Expression Regulation,
pubmed-meshheading:20159957-HeLa Cells,
pubmed-meshheading:20159957-Humans,
pubmed-meshheading:20159957-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:20159957-Liver,
pubmed-meshheading:20159957-Mice,
pubmed-meshheading:20159957-Mice, Inbred C57BL,
pubmed-meshheading:20159957-Mice, Knockout,
pubmed-meshheading:20159957-Orphan Nuclear Receptors,
pubmed-meshheading:20159957-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:20159957-Small Ubiquitin-Related Modifier Proteins
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pubmed:year |
2010
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pubmed:articleTitle |
GPS2-dependent corepressor/SUMO pathways govern anti-inflammatory actions of LRH-1 and LXRbeta in the hepatic acute phase response.
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pubmed:affiliation |
Center for Biosciences, Department of Biosciences and Nutrition, Karolinska Institutet, S-14157 Huddinge/Stockholm, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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