Inflammation Triggers Liver X Receptor-Dependent Lipogenesis.

Autor:	Liebergall SR; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Angdisen J; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Chan SH; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Chang Y; Institute for Fundamental Biomedical Research, Department of Medicine, Johns Hopkins University School of Medicine, St. Petersburg, Florida, USA., Osborne TF; Institute for Fundamental Biomedical Research, Department of Medicine, Johns Hopkins University School of Medicine, St. Petersburg, Florida, USA., Koeppel AF; Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Turner SD; Bioinformatics Core, University of Virginia School of Medicine, Charlottesville, Virginia, USA.; Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia, USA., Schulman IG; Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia, USA igs4c@virginia.edu.
Jazyk:	angličtina
Zdroj:	Molecular and cellular biology [Mol Cell Biol] 2020 Jan 03; Vol. 40 (2). Date of Electronic Publication: 2020 Jan 03 (Print Publication: 2020).
DOI:	10.1128/MCB.00364-19
Abstrakt:	Immune cell function can be modulated by changes in lipid metabolism. Our studies indicate that cholesterol and fatty acid synthesis increases in macrophages between 12 and 18 h after the activation of Toll-like receptors with proinflammatory stimuli and that the upregulation of lipogenesis may contribute to the resolution of inflammation. The inflammation-dependent increase in lipogenesis requires the induction of the liver X receptors, members of the nuclear receptor superfamily of transcription factors, by type I interferons in response to inflammatory signals. Instead of the well-established role for liver X receptors in stimulating cholesterol efflux, we demonstrate that liver X receptors are necessary for the proper resumption of cholesterol synthesis in response to inflammatory signals. Thus, liver X receptors function as bidirectional regulators of cholesterol homeostasis, driving efflux when cholesterol levels are high and facilitating synthesis in response to inflammatory signals. Liver X receptor activity is also required for the proper shutdown of a subset of type I interferon-stimulated genes as inflammation subsides, placing the receptors in a negative-feedback loop that may contribute to the resolution of the inflammatory response. (Copyright © 2020 American Society for Microbiology.)
Databáze:	MEDLINE
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