| Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a. | |
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MedLine Citation:
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PMID: 21531336 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We show that mice with a targeted deficiency in the gene encoding the lipogenic transcription factor SREBP-1a are resistant to endotoxic shock and systemic inflammatory response syndrome induced by cecal ligation and puncture (CLP). When macrophages from the mutant mice were challenged with bacterial lipopolysaccharide, they failed to activate lipogenesis as well as two hallmark inflammasome functions, activation of caspase-1 and secretion of IL-1β. We show that SREBP-1a activates not only genes required for lipogenesis in macrophages but also the gene encoding Nlrp1a, which is a core inflammasome component. Thus, SREBP-1a links lipid metabolism to the innate immune response, which supports our hypothesis that SREBPs evolved to regulate cellular reactions to external challenges that range from nutrient limitation and hypoxia to toxins and pathogens. |
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Authors:
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Seung-Soon Im; Leyla Yousef; Christoph Blaschitz; Janet Z Liu; Robert A Edwards; Stephen G Young; Manuela Raffatellu; Timothy F Osborne |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Cell metabolism Volume: 13 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-05-02 Completed Date: 2011-09-05 Revised Date: 2012-05-07 |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 540-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Metabolic Signaling and Disease Program, Sanford-Burnham Medical Research Institute, Orlando, FL 32827, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptor Proteins, Signal Transducing
/
antagonists & inhibitors,
genetics,
metabolism* Animals Apoptosis Regulatory Proteins / antagonists & inhibitors, genetics, metabolism* Blotting, Western Bone Marrow Caspase 1 / metabolism Cytokines / metabolism Enzyme Activation / drug effects Enzyme-Linked Immunosorbent Assay Immunity, Innate* Inflammasomes Interleukin-1beta / secretion Lipid Metabolism* Lipopolysaccharides / pharmacology Macrophages / cytology, immunology*, metabolism Male Mice Mice, Inbred C57BL Mice, Knockout RNA, Messenger / genetics RNA, Small Interfering / genetics Reverse Transcriptase Polymerase Chain Reaction Salmonella Infections / immunology*, metabolism, pathology Salmonella typhimurium / immunology Sterol Regulatory Element Binding Protein 1 / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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AI083619/AI/NIAID NIH HHS; AI083663/AI/NIAID NIH HHS; HL48044/HL/NHLBI NIH HHS; R01 AI083663-01A1/AI/NIAID NIH HHS; R01 HL048044-17/HL/NHLBI NIH HHS; R01 HL048044-19/HL/NHLBI NIH HHS; R21 AI083619-01/AI/NIAID NIH HHS; T32 AI60573/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adaptor Proteins, Signal Transducing; 0/Apoptosis Regulatory Proteins; 0/Cytokines; 0/Inflammasomes; 0/Interleukin-1beta; 0/Lipopolysaccharides; 0/NALP1 protein, mouse; 0/RNA, Messenger; 0/RNA, Small Interfering; 0/Srebf1 protein, mouse; 0/Sterol Regulatory Element Binding Protein 1; EC 3.4.22.36/Caspase 1 |
| Comments/Corrections | |
Comment In:
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Nat Rev Immunol. 2011 Jun;11(6):368-9
[PMID:
21610734
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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