High-Density Lipoproteins Exert Pro-inflammatory Effects on Macrophages via Passive Cholesterol Depletion and PKC-NF-kappa B/STAT1-IRF1 Signaling
In: Cell metabolism, Jg. 25 (2017-01-10), Heft 1, S. 197-207
Online
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Zugriff:
Item does not contain fulltext Membrane cholesterol modulates a variety of cell signaling pathways and functions. While cholesterol depletion by high-density lipoproteins (HDLs) has potent anti-inflammatory effects in various cell types, its effects on inflammatory responses in macrophages remain elusive. Here we show overt pro-inflammatory effects of HDL-mediated passive cholesterol depletion and lipid raft disruption in murine and human primary macrophages in vitro. These pro-inflammatory effects were confirmed in vivo in peritoneal macrophages from apoA-I transgenic mice, which have elevated HDL levels. In line with these findings, the innate immune responses required for clearance of P. aeruginosa bacterial infection in lung were compromised in mice with low HDL levels. Expression analysis, ChIP-PCR, and combinatorial pharmacological and genetic intervention studies unveiled that both native and reconstituted HDL enhance Toll-like-receptor-induced signaling by activating a PKC-NF-kappaB/STAT1-IRF1 axis, leading to increased inflammatory cytokine expression. HDL's pro-inflammatory activity supports proper functioning of macrophage immune responses.
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High-Density Lipoproteins Exert Pro-inflammatory Effects on Macrophages via Passive Cholesterol Depletion and PKC-NF-kappa B/STAT1-IRF1 Signaling
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| Autor/in / Beteiligte Person: | Schalkwijk, Casper G. ; Huitema, Leonie F. A. ; Touqui, Lhousseine ; Marion J.J. Gijbels ; Rye, Kerry-Anne ; Abdollahi-Roodsaz, Shahla ; Donners, Marjo M. P. C. ; Emiel P. C. van der Vorst ; Theodorou, Kosta ; Wolfs, Ine M. J. ; Debby P.Y. Koonen ; Bursill, Christina A. ; Menno P.J. de Winther ; Hoeksema, Marten A. ; Leitges, Michael ; Goossens, Pieter ; Plat, Jogchum ; Marijke J.E. Kuijpers ; Tas, Sander W. ; Lawrence, Toby ; Aliyev, Taghi ; Erik A.L. Biessen ; Wu, Yongzheng ; Chih Chieh Wang ; Miranda Van Eck ; McDaniels, Kimberly R. ; Biologie cellulaire de l'Infection microbienne - Cellular Biology of Microbial Infection ; Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) ; Centre d'Immunologie de Marseille - Luminy (CIML) ; Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) ; Laboratory for Metabolism and Vascular Medicine ; Academic Hospital Maastricht ; Department of rheumatology ; Radboud University [Nijmegen] ; Biotechnology center of Oslo ; Faculty of Medicine [Oslo] ; University of Oslo (UiO)-University of Oslo (UiO)-Rigshospitalet [Copenhagen] ; Copenhagen University Hospital-Copenhagen University Hospital ; Biology, Human ; Division of Biopharmaceutics ; Leiden, Universiteit ; Heart Research Institute ; Institut Pasteur [Paris] (IP) ; Mucoviscidose et bronchopathies chroniques : biopathologie et phénotypes cliniques (EA 2511) ; Hôpital Cochin [AP-HP] ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5) ; Biologie cellulaire de l'Infection microbienne ; Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU) ; Radboud university [Nijmegen] ; Universiteit Leiden [Leiden] ; Institut Pasteur [Paris] ; CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5) ; Promovendi, CD ; Pathologie ; RS: CARIM - R3.06 - The vulnerable plaque: makers and markers ; Ondersteunend personeel, CD ; Biochemie ; Genetica, Moleculaire ; RS: CARIM - R3.01 - Vascular complications of diabetes and the metabolic syndrome ; Geneeskunde, Interne ; RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health ; RS: NUTRIM - HB/BW section, B ; RS: NUTRIM - R1 - Metabolic Syndrome ; Center for Liver, Digestive and Metabolic Diseases (CLDM) ; Cardiovascular Centre (CVC) ; School, Graduate ; Biochemistry, Medical ; AII - Inflammatory diseases ; ACS - Amsterdam Cardiovascular Sciences ; Clinical Immunology and Rheumatology ; AII - Amsterdam institute for Infection and Immunity ; ACS - Atherosclerosis & ischemic syndromes |
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| Zeitschrift: | Cell metabolism, Jg. 25 (2017-01-10), Heft 1, S. 197-207 |
| Veröffentlichung: | CELL PRESS, 2017 |
| Medientyp: | unknown |
| ISSN: | 1550-4131 (print) |
| DOI: | 10.1016/j.cmet.2016.10.013 |
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