High-Density Lipoproteins Exert Pro-inflammatory Effects on Macrophages via Passive Cholesterol Depletion and PKC-NF-kappa B/STAT1-IRF1 Signaling
Emiel P. C. van Der Vorst
,
Kosta Theodorou
,
Yongzheng Wu
(1)
,
Marten A. Hoeksema
,
Pieter Goossens
(2)
,
Christina A. Bursill
,
Taghi Aliyev
,
Leonie F. A. Huitema
,
Sander W. Tas
,
Ine M. J. Wolfs
,
Marijke J. E. Kuijpers
,
Marion J. Gijbels
,
Casper G. Schalkwijk
(3)
,
Debby P. Y. Koonen
,
Shahla Abdollahi-Roodsaz
(4)
,
Kimberly Mcdaniels
,
Chih-Chieh Wang
,
Michael Leitges
(5)
,
Toby Lawrence
(2)
,
Jogchum Plat
(6)
,
Miranda van Eck
(7)
,
Kerry-Anne Rye
(8)
,
Lhousseine Touqui
(9, 10)
,
Menno P. J. De Winther
,
Erik A. L. Biessen
,
Marjo M. P. C. Donners
1
Biologie cellulaire de l'Infection microbienne - Cellular Biology of Microbial Infection
2 CIML - Centre d'Immunologie de Marseille - Luminy
3 Laboratory for Metabolism and Vascular Medicine
4 Department of rheumatology
5 Biotechnology center of Oslo
6 Human Biology
7 Division of Biopharmaceutics
8 Heart Research Institute
9 IP - Institut Pasteur [Paris]
10 EA 2511 - Mucoviscidose et bronchopathies chroniques : biopathologie et phénotypes cliniques
2 CIML - Centre d'Immunologie de Marseille - Luminy
3 Laboratory for Metabolism and Vascular Medicine
4 Department of rheumatology
5 Biotechnology center of Oslo
6 Human Biology
7 Division of Biopharmaceutics
8 Heart Research Institute
9 IP - Institut Pasteur [Paris]
10 EA 2511 - Mucoviscidose et bronchopathies chroniques : biopathologie et phénotypes cliniques
Emiel P. C. van Der Vorst
- Fonction : Auteur
Kosta Theodorou
- Fonction : Auteur
Yongzheng Wu
- Fonction : Auteur
- PersonId : 734669
- IdHAL : wuyzh
- ORCID : 0000-0003-0050-8480
- IdRef : 089425936
Marten A. Hoeksema
- Fonction : Auteur
Christina A. Bursill
- Fonction : Auteur
Taghi Aliyev
- Fonction : Auteur
Leonie F. A. Huitema
- Fonction : Auteur
Sander W. Tas
- Fonction : Auteur
Ine M. J. Wolfs
- Fonction : Auteur
Marijke J. E. Kuijpers
- Fonction : Auteur
Marion J. Gijbels
- Fonction : Auteur
Debby P. Y. Koonen
- Fonction : Auteur
Kimberly Mcdaniels
- Fonction : Auteur
Chih-Chieh Wang
- Fonction : Auteur
Toby Lawrence
- Fonction : Auteur
- PersonId : 17180
- IdHAL : toby-lawrence
- ORCID : 0000-0003-0967-6122
- IdRef : 184253942
Menno P. J. De Winther
- Fonction : Auteur
Erik A. L. Biessen
- Fonction : Auteur
Marjo M. P. C. Donners
- Fonction : Auteur
Résumé
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-kappa B/STAT1-IRF1 axis, leading to increased inflammatory cytokine expression. HDL's pro-inflammatory activity supports proper functioning of macrophage immune responses.
Domaines
ImmunologieFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
High-Density Lipoproteins Exert Pro-inflammatory Effects on Macrophages via Passive Cholesterol Depletion and PKC-NF-kappa B/STAT1-IRF1 Signaling
|
Résumé |
en
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-kappa B/STAT1-IRF1 axis, leading to increased inflammatory cytokine expression. HDL's pro-inflammatory activity supports proper functioning of macrophage immune responses.
|
Auteur(s) |
Emiel P. C. van Der Vorst
, Kosta Theodorou
, Yongzheng Wu
1
, Marten A. Hoeksema
, Pieter Goossens
2
, Christina A. Bursill
, Taghi Aliyev
, Leonie F. A. Huitema
, Sander W. Tas
, Ine M. J. Wolfs
, Marijke J. E. Kuijpers
, Marion J. Gijbels
, Casper G. Schalkwijk
3
, Debby P. Y. Koonen
, Shahla Abdollahi-Roodsaz
4
, Kimberly Mcdaniels
, Chih-Chieh Wang
, Michael Leitges
5
, Toby Lawrence
2
, Jogchum Plat
6
, Miranda van Eck
7
, Kerry-Anne Rye
8
, Lhousseine Touqui
9, 10
, Menno P. J. De Winther
, Erik A. L. Biessen
, Marjo M. P. C. Donners
1
Biologie cellulaire de l'Infection microbienne - Cellular Biology of Microbial Infection
( 462720 )
- Département de Biologie cellulaire et Infection, 25-28, rue du docteur Roux, 75724 Paris Cedex 15
- France
2
CIML -
Centre d'Immunologie de Marseille - Luminy
( 182245 )
- Parc scientifique et technologique de Luminy - 163, avenue de Luminy - Case 906 - 13288 Marseille cedex 09
- France
3
Laboratory for Metabolism and Vascular Medicine
( 141763 )
- Maastricht
- Pays-Bas
4
Department of rheumatology
( 181577 )
- Nijmegen Medical Center
- Pays-Bas
5
Biotechnology center of Oslo
( 48512 )
- Norvège
6
Human Biology
( 126798 )
- Pays-Bas
7
Division of Biopharmaceutics
( 60354 )
- Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden University, The Netherlands
- Pays-Bas
8
Heart Research Institute
( 99606 )
- Sydney
- Australie
9
IP -
Institut Pasteur [Paris]
( 300027 )
- 25-28, rue du docteur Roux, 75724 Paris cedex 15
- France
10
EA 2511 -
Mucoviscidose et bronchopathies chroniques : biopathologie et phénotypes cliniques
( 411657 )
- Faculté de médecine Paris Descartes – Site Cochin
24 rue du faubourg Saint Jacques 75014 PARIS
- France
|
Volume |
25
|
Numéro |
1
|
Page/Identifiant |
197-207
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2017-01-10
|
Domaine(s) |
|
DOI | 10.1016/j.cmet.2016.10.013 |
Pubmed Id | 27866837 |
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