title: High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3.
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.
authors: 1] Institute of Innate Immunity, University Hospitals, Biomedical Centre, University of Bonn, Bonn, Germany. [2].
authors: Dominic
authors: D
authors: De Nardo
authors: 1] Institute of Innate Immunity, University Hospitals, Biomedical Centre, University of Bonn, Bonn, Germany. [2].
authors: Larisa I
authors: LI
authors: Labzin
authors: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors: Hajime
authors: H
authors: Kono
authors: Department of Clinical Laboratory Science, Teikyo University Faculty of Medical Technology, Tokyo, Japan.
authors: Reiko
authors: R
authors: Seki
authors: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors: Susanne V
authors: SV
authors: Schmidt
authors: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors: Marc
authors: M
authors: Beyer
authors: 1] Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia. [2] Institute of Ageing Research, Hangzhou Normal University School of Medicine, Hangzhou, China.
authors: Dakang
authors: D
authors: Xu
authors: Department of Medicine/Cardiology, University of Bonn, Bonn, Germany.
authors: Sebastian
authors: S
authors: Zimmer
authors: Department of Medicine/Cardiology, University of Bonn, Bonn, Germany.
authors: Catharina
authors: C
authors: Lahrmann
authors: Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn, Germany.
authors: Frank A
authors: FA
authors: Schildberg
authors: Institute of Innate Immunity, University Hospitals, Biomedical Centre, University of Bonn, Bonn, Germany.
authors: Johanna
authors: J
authors: Vogelhuber
authors: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors: Michael
authors: M
authors: Kraut
authors: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors: Thomas
authors: T
authors: Ulas
authors: Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
authors: Anja
authors: A
authors: Kerksiek
authors: Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
authors: Wolfgang
authors: W
authors: Krebs
authors: Department of Medicine/Cardiology, University of Bonn, Bonn, Germany.
authors: Niklas
authors: N
authors: Bode
authors: Institute of Innate Immunity, University Hospitals, Biomedical Centre, University of Bonn, Bonn, Germany.
authors: Alena
authors: A
authors: Grebe
authors: Lipid Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Michael L
authors: ML
authors: Fitzgerald
authors: Lipid Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Nicholas J
authors: NJ
authors: Hernandez
authors: Monash Institute of Medical Research, Monash University, Melbourne, Victoria, Australia.
authors: Bryan R G
authors: 0000000249691151
authors: BR
authors: Williams
authors: 1] Institutes of Molecular Medicine and Experimental Immunology, University of Bonn, Bonn, Germany. [2] Institute of Molecular Immunology, Technical University of Munich, Munich, Germany.
authors: Percy
authors: P
authors: Knolle
authors: 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.
authors: Manfred
authors: M
authors: Kneilling
authors: Department of Dermatology, Eberhard Karls University, Tuebingen, Germany.
authors: Martin
authors: M
authors: Röcken
authors: Institute for Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn, Germany.
authors: Dieter
authors: D
authors: Lütjohann
authors: Cardiovascular Therapeutics, CSL Limited, Parkville, Australia.
authors: Samuel D
authors: SD
authors: Wright
authors: 1] Life and Medical Sciences Institute, University of Bonn, Bonn, Germany. [2].
authors: Joachim L
authors: JL
authors: Schultze
authors: 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].
authors: Eicke
authors: E
authors: Latz
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000628:therapy*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007249:Inflammation / Q000628:therapy*; D008075:Lipoproteins, HDL / Q000494:pharmacology / Q000627:therapeutic use*; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D049490:Systems Biology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology
chemical_list: D051700:Activating Transcription Factor 3; D000894:Anti-Inflammatory Agents, Non-Steroidal; C103002:Atf3 protein, mouse; D016207:Cytokines; D008075:Lipoproteins, HDL; D051197:Toll-Like Receptor 4; D002784:Cholesterol