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Nat Immunol. 2014 Feb;15(2):152-60. doi: 10.1038/ni.2784. Epub 2013 Dec 8.

High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3.

Author information

1
1] Institute of Innate Immunity, University Hospitals, Biomedical Centre, University of Bonn, Bonn, Germany. [2].
2
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
3
Department of Clinical Laboratory Science, Teikyo University Faculty of Medical Technology, Tokyo, Japan.
4
Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
5
1] Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia. [2] Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, China.
6
Department of Medicine/Cardiology, University of Bonn, Bonn, Germany.
7
Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn, Germany.
8
Institute of Innate Immunity, University Hospitals, Biomedical Centre, University of Bonn, Bonn, Germany.
9
Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
10
Lipid Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
11
Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia.
12
1] Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn, Germany. [2] Institute of Molecular Immunology, Technical University of Munich, Munich, Germany.
13
1] Department of Dermatology, Eberhard Karls University, Tuebingen, Germany. [2] Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy, Eberhard Karls University, Tuebingen, Germany.
14
Department of Dermatology, Eberhard Karls University, Tuebingen, Germany.
15
Cardiovascular Therapeutics, CSL Limited, Parkville, Australia.
16
1] Life and Medical Sciences Institute, University of Bonn, Bonn, Germany. [2].
17
1] Institute of Innate Immunity, University Hospitals, Biomedical Centre, University of Bonn, Bonn, Germany. [2] Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, Massachusetts, USA. [3] German Center for Neurodegenerative Diseases, Bonn, Germany. [4].

Abstract

High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, particularly in immune cells such as macrophages, remain poorly understood. Here we identify the transcriptional regulator ATF3, as an HDL-inducible target gene in macrophages that downregulates the expression of Toll-like receptor (TLR)-induced proinflammatory cytokines. The protective effects of HDL against TLR-induced inflammation were fully dependent on ATF3 in vitro and in vivo. Our findings may explain the broad anti-inflammatory and metabolic actions of HDL and provide the basis for predicting the success of new HDL-based therapies.

PMID:
24317040
PMCID:
PMC4009731
DOI:
10.1038/ni.2784
[Indexed for MEDLINE]
Free PMC Article

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