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

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 re...

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Vydané v:	Cell metabolism Ročník 25; číslo 2; s. 412
Hlavní autori:	Oishi, Yumiko, Spann, Nathanael J, Link, Verena M, Muse, Evan D, Strid, Tobias, Edillor, Chantle, Kolar, Matthew J, Matsuzaka, Takashi, Hayakawa, Sumio, Tao, Jenhan, Kaikkonen, Minna U, Carlin, Aaron F, Lam, Michael T, Manabe, Ichiro, Shimano, Hitoshi, Saghatelian, Alan, Glass, Christopher K
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 07.02.2017
Predmet:	Animals Base Sequence Biosynthetic Pathways - drug effects Biosynthetic Pathways - genetics Enhancer Elements, Genetic - genetics Fatty Acids - metabolism Inflammation - genetics Inflammation - pathology Lipid Metabolism - drug effects Lipopolysaccharides - pharmacology Liver X Receptors - metabolism Macrophages - drug effects Macrophages - metabolism Male Mice, Inbred C57BL Phenotype Signal Transduction - drug effects Sterol Regulatory Element Binding Protein 1 - metabolism Time Factors Toll-Like Receptor 4 - metabolism innate immunity unsaturated fatty acids inflammation fatty acid metabolism transcriptional regulation EPA lipid metabolism SREBP1 DHA resolution
ISSN:	1932-7420, 1932-7420
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1932-7420 1932-7420
DOI:	10.1016/j.cmet.2016.11.009