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Haimerl, P. ; Bernhardt, U. ; Schindela, S. ; Henkel, F. ; Lechner, A. ; Zissler, U.M. ; Pastor, X. ; Thomas, D.* ; Cecil, A. ; Ge, Y.* ; Haid, M. ; Prehn, C. ; Tokarz, J. ; Heinig, M. ; Adamski, J. ; Schmidt-Weber, C.B. ; Chaker, A. ; Esser-von Bieren, J.

Inflammatory macrophage memory in nonsteroidal anti-inflammatory drug–exacerbated respiratory disease.

J. Allergy Clin. Immunol. 147, 587-599 (2020)
Verlagsversion Postprint DOI PMC
Open Access Green
Background: Nonsteroidal anti-inflammatory drug–exacerbated respiratory disease (N-ERD) is a chronic inflammatory condition, which is driven by an aberrant arachidonic acid metabolism. Macrophages are major producers of arachidonic acid metabolites and subject to metabolic reprogramming, but they have been neglected in N-ERD. Objective: This study sought to elucidate a potential metabolic and epigenetic macrophage reprogramming in N-ERD. Methods: Transcriptional, metabolic, and lipid mediator profiles in macrophages from patients with N-ERD and healthy controls were assessed by RNA sequencing, Seahorse assays, and LC-MS/MS. Metabolites in nasal lining fluid, sputum, and plasma from patients with N-ERD (n = 15) and healthy individuals (n = 10) were quantified by targeted metabolomics analyses. Genome-wide methylomics were deployed to define epigenetic mechanisms of macrophage reprogramming in N-ERD. Results: This study shows that N-ERD monocytes/macrophages exhibit an overall reduction in DNA methylation, aberrant metabolic profiles, and an increased expression of chemokines, indicative of a persistent proinflammatory activation. Differentially methylated regions in N-ERD macrophages included genes involved in chemokine signaling and acylcarnitine metabolism. Acylcarnitines were increased in macrophages, sputum, nasal lining fluid, and plasma of patients with N-ERD. On inflammatory challenge, N-ERD macrophages produced increased levels of acylcarnitines, proinflammatory arachidonic acid metabolites, cytokines, and chemokines as compared to healthy macrophages. Conclusions: Together, these findings decipher a proinflammatory metabolic and epigenetic reprogramming of macrophages in N-ERD.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Acylcarnitines ; Chemokines ; Eicosanoids ; Lipid Mediator ; Macrophages ; Metabolomics ; Nasal Polyps ; Nsaid-exacerbated Respiratory Disease ; Trained Immunity ; Type 2 Inflammation
Sprache englisch
Veröffentlichungsjahr 2020
HGF-Berichtsjahr 2020
ISSN (print) / ISBN 0091-6749
e-ISSN 1097-6825
Zeitschrift The journal of allergy and clinical immunology
Quellenangaben Band: 147, Heft: 2, Seiten: 587-599 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute for Allergy Research (IAF)
Institute of Computational Biology (ICB)
Molekulare Endokrinologie und Metabolismus (MEM)
POF Topic(s) 30202 - Environmental Health
30205 - Bioengineering and Digital Health
30201 - Metabolic Health
Forschungsfeld(er) Allergy
Enabling and Novel Technologies
Genetics and Epidemiology
PSP-Element(e) G-554600-001
G-505400-001
G-503800-001
G-505600-003
G-553500-001
Förderungen German Federal Ministry of Education and Research
German Center for Lung Research
Helmholtz Young Investigator grant
Fritz Thyssen Stiftung
German Research Foundation
Else Kroner-Fresenius-Stiftung
DOI 10.1016/j.jaci.2020.04.064
WOS ID WOS:000616665800021
Scopus ID 85088212142
PubMed ID 32540397
Erfassungsdatum 2020-07-07
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