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SREBP1 Contributes to Resolution of Pro-inflammatory TLR4 Signaling by Reprogramming Fatty Acid Metabolism

Oishi, Yumiko (författare)
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
Spann, Nathanael J (författare)
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Link, Verena M (författare)
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
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Muse, Evan D (författare)
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
Strid, Tobias (författare)
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Edillor, Chantle (författare)
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Kolar, Matthew J (författare)
Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Matsuzaka, Takashi (författare)
Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, Graduate School of Comprehensive Human Sciences, International Institute for Integrative Sleep Medicine (WPI-IIIS), and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki Prefecture 305-8571, Japan
Hayakawa, Sumio (författare)
Department of Cellular and Molecular Medicine, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
Tao, Jenhan (författare)
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Kaikkonen, Minna U (författare)
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA // Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, 70211 Kuopio, Finland
Carlin, Aaron F (författare)
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Lam, Michael T (författare)
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
Manabe, Ichiro (författare)
Department of Aging Research, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan
Shimano, Hitoshi (författare)
Department of Internal Medicine (Endocrinology and Metabolism), Faculty of Medicine, Graduate School of Comprehensive Human Sciences, International Institute for Integrative Sleep Medicine (WPI-IIIS), and Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki Prefecture 305-8571, Japan
Saghatelian, Alan (författare)
Salk Institute for Biological Studies, La Jolla, CA 92037, USA
Glass, Christopher K (författare)
Department of Cellular and Molecular Medicine, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA
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 (creator_code:org_t)
Cambridge, MA, United States : Cell Press, 2017
2017
Engelska.
Ingår i: Cell Metabolism. - Cambridge, MA, United States : Cell Press. - 1550-4131 .- 1932-7420. ; 25:2, s. 412-427
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

NATURVETENSKAP  -- Biologi -- Cellbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Cell Biology (hsv//eng)

Nyckelord

DHA
EPA
SREBP1
fatty acid metabolism
inflammation
innate immunity
lipid metabolism
resolution
transcriptional regulation
unsaturated fatty acids

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