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

The Journal of Allergy and Clinical Immunology
Pascal HaimerlJulia Esser-von Bieren

Abstract

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. Acylcarni...Continue Reading

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Citations

Oct 31, 2020·The Journal of Allergy and Clinical Immunology·Tanya M Laidlaw, Barbara Balestrieri
Jul 13, 2021·Frontiers in Genetics·Hoang Kim Tu TrinhHae-Sim Park
Sep 14, 2021·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·Constanze A JakwerthUlrich M Zissler
Nov 6, 2021·Current Opinion in Allergy and Clinical Immunology·Esha SehanobishElina Jerschow
Jan 3, 2022·The Journal of Allergy and Clinical Immunology·Antonie LechnerJulia Esser-von Bieren

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