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Publication : Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a.

First Author  Im SS Year  2011
Journal  Cell Metab Volume  13
Issue  5 Pages  540-9
PubMed ID  21531336 Mgi Jnum  J:175815
Mgi Id  MGI:5287349 Doi  10.1016/j.cmet.2011.04.001
Citation  Im SS, et al. (2011) Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a. Cell Metab 13(5):540-9
abstractText  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-1beta. 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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