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SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA // Department of Cellular and Molecular Medicine, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA // Department II, Faculty of Biology, Ludwig-Maximilians Universität München, Planegg-Martinsried 82152, Germany.
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA // Scripps Translational Science Institute, La Jolla, CA 92037, USA.
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2017 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 25, no 2, p. 412-427, article id S1550-4131(16)30588-5Article in journal (Refereed) Published
Abstract [en]

Macrophages play pivotal roles in both the induction and resolution phases of inflammatory processes. Macrophages have been shown to synthesize anti-inflammatory fatty acids in an LXR-dependent manner, but whether the production of these species contributes to the resolution phase of inflammatory responses has not been established. Here, we identify a biphasic program of gene expression that drives production of anti-inflammatory fatty acids 12-24 hr following TLR4 activation and contributes to downregulation of mRNAs encoding pro-inflammatory mediators. Unexpectedly, rather than requiring LXRs, this late program of anti-inflammatory fatty acid biosynthesis is dependent on SREBP1 and results in the uncoupling of NFκB binding from gene activation. In contrast to previously identified roles of SREBP1 in promoting production of IL1β during the induction phase of inflammation, these studies provide evidence that SREBP1 also contributes to the resolution phase of TLR4-induced gene activation by reprogramming macrophage lipid metabolism.

Place, publisher, year, edition, pages
Cambridge, MA, United States: Cell Press , 2017. Vol. 25, no 2, p. 412-427, article id S1550-4131(16)30588-5
Keywords [en]
DHA, EPA, SREBP1, fatty acid metabolism, inflammation, innate immunity, lipid metabolism, resolution, transcriptional regulation, unsaturated fatty acids
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:liu:diva-154610DOI: 10.1016/j.cmet.2016.11.009ISI: 000396354400021PubMedID: 28041958Scopus ID: 2-s2.0-85009374100OAI: oai:DiVA.org:liu-154610DiVA, id: diva2:1290789
Available from: 2019-02-21 Created: 2019-02-21 Last updated: 2019-03-08Bibliographically approved

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