@article{fa776f46f8004f9bb4032900a26e48a9,
title = "Linking lipid metabolism to the innate immune response in macrophages through sterol regulatory element binding protein-1a",
abstract = "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.",
author = "Im, {Seung Soon} and Leyla Yousef and Christoph Blaschitz and Liu, {Janet Z.} and Edwards, {Robert A.} and Young, {Stephen G.} and Manuela Raffatellu and Osborne, {Timothy F.}",
note = "Funding Information: We thank Dr. Linda Hammond for contributions to the early portions of this work, Dr. Craig Walsh for helpful discussions, and laboratory members for comments on the project. We thank Vanessa Arias and Dr. Andrea Tenner for assistance with macrophage culture, Dr. Dat Tran for assistance with the CLP procedure, Peter Phelan for technical assistance, and Dr. Young-Kyo Seo for preparing the SREBP-1 antibody. We also acknowlege the UCI microarray facility for technical assistance and Sang-Hee Yuh for analysis of microarray data. This manuscript was also significantly improved by comments from the anonymous reviewers (especially reviewer 2). This study was supported in part by grants from the National Institutes of Health (NIH) to T.F.O. (HL48044) and M.R. (AI083619, AI083663). M.R. is the recipient of an IDSA ERF/NIFID Astellas Young Investigator Award. J.Z.L. is supported by NIH Immunology Research Training Program grant NIH T32 AI60573. S.-S.I., L.Y., C.B., and J.Z.L. performed experiments; R.A.E. performed the histopathological analysis; S.G.Y. provided key reagents; S.-S.I., M.R., R.A.E., and T.F.O. designed experiments and analyzed data; and S.-S.I., S.G.Y., M.R., and T.F.O. wrote the manuscript. ",
year = "2011",
month = may,
day = "4",
doi = "10.1016/j.cmet.2011.04.001",
language = "English (US)",
volume = "13",
pages = "540--549",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "5",
}