A Defective Pentose Phosphate Pathway Reduces Inflammatory Macrophage Responses during Hypercholesterolemia

被引：147

作者：

Baardman, Jeroen ^{[1
]}

Verberk, Sanne G. S. ^{[2
]}

Prange, Koen H. M. ^{[1
]}

van Weeghel, Michel ^{[3
]}

van der Velden, Saskia ^{[1
]}

Ryan, Dylan G. ^{[4
]}

Wust, Rob C. I. ^{[3
,5
]}

Neele, Annette E. ^{[1
]}

Speijer, Dave ^{[1
]}

Denis, Simone W. ^{[3
]}

Witte, Maarten E. ^{[2
]}

Houtkooper, Riekelt H. ^{[3
]}

O'neill, Luke A. ^{[4
]}

Knatko, Elena V. ^{[6
]}

Dinkova-Kostova, Albena T. ^{[6
,7
]}

Lutgens, Esther ^{[1
,8
]}

de Winther, Menno P. J. ^{[1
,8
]}

Van den Bossche, Jan ^{[1
,2
]}

机构：

[1] Univ Amsterdam, Amsterdam UMC, Dept Med Biochem, Expt Vasc Biol,Amsterdam Cardiovasc Sci, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[2] Vrije Univ Amsterdam, Amsterdam UMC, Dept Mol Cell Biol & Immunol, Amsterdam Cardiovasc Sci,Canc Ctr Amsterdam, Boelelaan 1117, NL-1081 HZ Amsterdam, Netherlands

[3] Univ Amsterdam, Amsterdam UMC, Lab Genet Metab Dis, Amsterdam Cardiovasc Sci, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[4] Trinity Coll Dublin, Trinity Biomed Sci Inst, Sch Biochem & Immunol, Dublin 2, Ireland

[5] Univ Amsterdam, Amsterdam UMC, Dept Biomed Engn & Phys, Amsterdam Cardiovasc Sci, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[6] Univ Dundee, Sch Med, Div Cellular Med, Jacqui Wood Canc Ctr, Dundee DD1 9SY, Scotland

[7] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[8] Ludwig Maximilians Univ Munchen, Inst Cardiovasc Prevent IPEK, Pettenkoferstr 9, D-80336 Munich, Germany

来源：

CELL REPORTS | 2018年 / 25卷 / 08期

基金：

欧盟地平线“2020”;

关键词：

SUCCINATE-DEHYDROGENASE; NRF2; IMMUNOMETABOLISM; DYSFUNCTION; METABOLISM; ACTIVATION; ITACONATE; SIGNAL;

D O I：

10.1016/j.celrep.2018.10.092

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Metabolic reprogramming has emerged as a crucial regulator of immune cell activation, but how systemic metabolism influences immune cell metabolism and function remains to be investigated. To investigate the effect of dyslipidemia on immune cell metabolism, we performed in-depth transcriptional, metabolic, and functional characterization of macrophages isolated from hypercholesterolemic mice. Systemic metabolic changes in such mice alter cellular macrophage metabolism and attenuate inflammatory macrophage responses. In addition to diminished maximal mitochondrial respiration, hypercholesterolemia reduces the LPS-mediated induction of the pentose phosphate pathway (PPP) and the Nrf2-mediated oxidative stress response. Our observation that suppression of the PPP diminishes LPS-induced cytokine secretion supports the notion that this pathway contributes to inflammatory macrophage responses. Overall, this study reveals that systemic and cellular metabolism are strongly interconnected, together dictating macrophage phenotype and function.

引用

页码：2044 / +

页数：14

共 38 条

[1]

Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis [J].

Bambouskova, Monika ;

Gorvel, Laurent ;

Lampropoulou, Vicky ;

Sergushichev, Alexey ;

Loginicheva, Ekaterina ;

Johnson, Kendall ;

Korenfeld, Daniel ;

Mathyer, Mary Elizabeth ;

Kim, Hyeryun ;

Huang, Li-Hao ;

Duncan, Dustin ;

Bregman, Howard ;

Keskin, Abdurrahman ;

Santeford, Andrea ;

Apte, Rajendra S. ;

Sehgal, Raghav ;

Johnson, Britney ;

Amarasinghe, Gaya K. ;

Soares, Miguel P. ;

Satoh, Takashi ;

Akira, Shizuo ;

Hai, Tsonwin ;

Strong, Cristina de Guzman ;

Auclair, Karine ;

Roddy, Thomas P. ;

Biller, Scott A. ;

Jovanovic, Marko ;

Klechevsky, Eynav ;

Stewart, Kelly M. ;

Randolph, Gwendalyn J. ;

Artyomov, Maxim N. .

NATURE, 2018, 556 (7702) :501-+

[2]

STAR: ultrafast universal RNA-seq aligner [J].

Dobin, Alexander ;

Davis, Carrie A. ;

Schlesinger, Felix ;

Drenkow, Jorg ;

Zaleski, Chris ;

Jha, Sonali ;

Batut, Philippe ;

Chaisson, Mark ;

Gingeras, Thomas R. .

BIOINFORMATICS, 2013, 29 (01) :15-21

[3]

Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel [J].

Ference, Brian A. ;

Ginsberg, Henry N. ;

Graham, Ian ;

Ray, Kausik K. ;

Packard, Chris J. ;

Bruckert, Eric ;

Hegele, Robert A. ;

Krauss, Ronald M. ;

Raal, Frederick J. ;

Schunkert, Heribert ;

Watts, Gerald F. ;

Boren, Jan ;

Fazio, Sergio ;

Horton, Jay D. ;

Masana, Luis ;

Nicholls, Stephen J. ;

Nordestgaard, Borge G. ;

van de Sluis, Bart ;

Taskinen, Marja-Riitta ;

Tokgozoglu, Lale ;

Landmesser, Ulf ;

Laufs, Ulrich ;

Wiklund, Olov ;

Stock, Jane K. ;

Chapman, M. John ;

Catapano, Alberico L. .

EUROPEAN HEART JOURNAL, 2017, 38 (32) :2459-2472

[4]

Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARγ [J].

Ghisletti, Serena ;

Huang, Wendy ;

Ogawa, Sumito ;

Pascual, Gabriel ;

Lin, Mu-En ;

Willson, Timothy M. ;

Rosenfeld, Michael G. ;

Glass, Christopher K. .

MOLECULAR CELL, 2007, 25 (01) :57-70

[5]

Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell Identities [J].

Heinz, Sven ;

Benner, Christopher ;

Spann, Nathanael ;

Bertolino, Eric ;

Lin, Yin C. ;

Laslo, Peter ;

Cheng, Jason X. ;

Murre, Cornelis ;

Singh, Harinder ;

Glass, Christopher K. .

MOLECULAR CELL, 2010, 38 (04) :576-589

[6]

Divergence of spatial gene expression profiles following species-specific gene duplications in human and mouse [J].

Huminiecki, L ;

Wolfe, KH .

GENOME RESEARCH, 2004, 14 (10A) :1870-1879

[7]

An Nrf2 small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements [J].

Itoh, K ;

Chiba, T ;

Takahashi, S ;

Ishii, T ;

Igarashi, K ;

Katoh, Y ;

Oyake, T ;

Hayashi, N ;

Satoh, K ;

Hatayama, I ;

Yamamoto, M ;

Nabeshima, Y .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 236 (02) :313-322

[8]

Network Integration of Parallel Metabolic and Transcriptional Data Reveals Metabolic Modules that Regulate Macrophage Polarization [J].

Jha, Abhishek K. ;

Huang, Stanley Ching-Cheng ;

Sergushichev, Alexey ;

Lampropoulou, Vicky ;

Ivanova, Yulia ;

Loginicheva, Ekaterina ;

Chmielewski, Karina ;

Stewart, Kelly M. ;

Ashall, Juliet ;

Everts, Bart ;

Pearce, Edward J. ;

Driggers, Edward M. ;

Artyomov, Maxim N. .

IMMUNITY, 2015, 42 (03) :419-430

[9]

Identification of a Novel Macrophage Phenotype That Develops in Response to Atherogenic Phospholipids via Nrf2 [J].

Kadl, Alexandra ;

Meher, Akshaya K. ;

Sharma, Poonam R. ;

Lee, Monica Y. ;

Doran, Amanda C. ;

Johnstone, Scott R. ;

Elliott, Michael R. ;

Gruber, Florian ;

Han, Jenny ;

Chen, Wenshu ;

Kensler, Thomas ;

Ravichandran, Kodi S. ;

Isakson, Brant E. ;

Wamhoff, Brian R. ;

Leitinger, Norbert .

CIRCULATION RESEARCH, 2010, 107 (06) :737-U155

[10]

Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription [J].

Kobayashi, Eri H. ;

Suzuki, Takafumi ;

Funayama, Ryo ;

Nagashima, Takeshi ;

Hayashi, Makiko ;

Sekine, Hiroki ;

Tanaka, Nobuyuki ;

Moriguchi, Takashi ;

Motohashi, Hozumi ;

Nakayama, Keiko ;

Yamamoto, Masayuki .

NATURE COMMUNICATIONS, 2016, 7

← 1 2 3 4 →