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

BackgroundNonsteroidal anti-inflammatory drug–exacerbated respiratory disease (N-ERD) is a chronic inflammatory condition, which driven by an aberrant arachidonic acid metabolism. Macrophages are major producers of metabolites and subject to metabolic reprogramming, but they have been neglected in N-ERD.ObjectiveThis study sought elucidate potential epigenetic macrophage reprogramming N-ERD.MethodsTranscriptional, metabolic, lipid mediator profiles macrophages from patients with N-ERD healthy controls were assessed RNA sequencing, Seahorse assays, LC-MS/MS. Metabolites nasal lining fluid, sputum, plasma (n = 15) individuals 10) quantified targeted metabolomics analyses. Genome-wide methylomics deployed define mechanisms N-ERD.ResultsThis shows that monocytes/macrophages exhibit overall reduction DNA methylation, profiles, increased expression chemokines, indicative persistent proinflammatory activation. Differentially methylated regions included genes involved chemokine signaling acylcarnitine Acylcarnitines macrophages, N-ERD. On challenge, produced levels acylcarnitines, metabolites, cytokines, chemokines as compared macrophages.ConclusionsTogether, these findings decipher Nonsteroidal This Transcriptional, macrophages. Together,