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

Anti-Inflammatory Agents, Non-Steroidal / adverse effects Asthma / chemically induced Humans Immunologic Memory / immunology Macrophage Activation / immunology Macrophages / immunology Nasal Polyps / chemically induced
Acylcarnitines NSAID-exacerbated respiratory disease chemokines eicosanoids lipid mediator macrophages metabolomics nasal polyps trained immunity type 2 inflammation

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
02 2021
Historique:
received: 13 02 2020
revised: 04 04 2020
accepted: 22 04 2020
pubmed: 17 6 2020
medline: 14 9 2021
entrez: 17 6 2020
Statut: ppublish

Résumé

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. This study sought to elucidate a potential metabolic and epigenetic macrophage reprogramming in N-ERD. 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. 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. Together, these findings decipher a proinflammatory metabolic and epigenetic reprogramming of macrophages in N-ERD.

Sections du résumé

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.

Identifiants

DOI: 10.1016/j.jaci.2020.04.064 PMID: 32540397
pubmed: 32540397
pii: S0091-6749(20)30803-4
doi: 10.1016/j.jaci.2020.04.064
pii:
doi:

Substances chimiques

Anti-Inflammatory Agents, Non-Steroidal 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

587-599

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Auteurs

Pascal Haimerl (P)

Center of Allergy and Environment, Technical University of Munich and Helmholtz Zentrum München, Munich, Germany.

Ulrike Bernhardt (U)

Center of Allergy and Environment, Technical University of Munich and Helmholtz Zentrum München, Munich, Germany; Department of Otolaryngology, Allergy Section, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

Sonja Schindela (S)

Center of Allergy and Environment, Technical University of Munich and Helmholtz Zentrum München, Munich, Germany.

Fiona D R Henkel (FDR)

Center of Allergy and Environment, Technical University of Munich and Helmholtz Zentrum München, Munich, Germany.

Antonie Lechner (A)

Center of Allergy and Environment, Technical University of Munich and Helmholtz Zentrum München, Munich, Germany.

Ulrich M Zissler (UM)

Center of Allergy and Environment, Technical University of Munich and Helmholtz Zentrum München, Munich, Germany.

Xavier Pastor (X)

Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.

Dominique Thomas (D)

Pharmazentrum Frankfurt/Zentrum für Arzneimittelforschung, -Entwicklung und -Sicherheit (ZAFES), Institute of Clinical Pharmacology, Goethe University Frankfurt, Frankfurt, Germany.

Alexander Cecil (A)

Research Unit of Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.

Yan Ge (Y)

Biotechnology Center Dresden, Technical University of Dresden, Dresden, Germany.

Mark Haid (M)

Research Unit of Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.

Cornelia Prehn (C)

Research Unit of Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany.

Janina Tokarz (J)

Research Unit of Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research, Neuherberg, Germany.

Matthias Heinig (M)

Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.

Jerzy Adamski (J)

Research Unit of Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, Neuherberg, Germany; Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Carsten B Schmidt-Weber (CB)

Center of Allergy and Environment, Technical University of Munich and Helmholtz Zentrum München, Munich, Germany.

Adam M Chaker (AM)

Center of Allergy and Environment, Technical University of Munich and Helmholtz Zentrum München, Munich, Germany; Department of Otolaryngology, Allergy Section, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.

Julia Esser-von Bieren (J)

Center of Allergy and Environment, Technical University of Munich and Helmholtz Zentrum München, Munich, Germany. Electronic address: Julia.esser-von-bieren@tum.de.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antirhumatismaux › Anti-inflammatoires non stéroïdiens › Inflammatory macrophage memory in nonsteroidal...
questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Hypersensibilité respiratoire › Asthme › Inflammatory macrophage memory in nonsteroidal...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Inflammatory macrophage memory in nonsteroidal...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité acquise › Mémoire immunologique › Inflammatory macrophage memory in nonsteroidal...
questionsmedicales.fr › Phénomènes du système immunitaire › Cytotoxicité immunologique › Activation des macrophages › Inflammatory macrophage memory in nonsteroidal...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Inflammatory macrophage memory in nonsteroidal...
questionsmedicales.fr › États, signes et symptômes pathologiques › États anatomopathologiques › Polypes › Polypes du nez › Inflammatory macrophage memory in nonsteroidal...