title: Aspirin induces IL-4 production: augmented IL-4 production in aspirin-exacerbated respiratory disease.
abstract: Aspirin hypersensitivity is a hallmark of aspirin-exacerbated respiratory disease (AERD), a clinical syndrome characterized by the severe inflammation of the respiratory tract after ingestion of cyclooxygenase-1 inhibitors. We investigated the capacity of aspirin to induce interleukin-4 (IL-4) production in inflammatory cells relevant to AERD pathogenesis and examined the associated biochemical and molecular pathways. We also compared IL-4 production in peripheral blood mononuclear cells (PBMCs) from patients with AERD vs aspirin-tolerant asthma (ATA) upon exposure to aspirin. Aspirin induced IL-4 expression and activated the IL-4 promoter in a report assay. The capacity of aspirin to induce IL-4 expression correlated with its activity to activate mitogen-activated protein kinases, to form DNA-protein complexes on P elements in the IL-4 promoter and to synthesize nuclear factor of activated T cells, critical transcription factors for IL-4 transcription. Of clinical importance, aspirin upregulated IL-4 production twice as much in PBMCs from patients with AERD compared with PBMCs from patients with ATA. Our results suggest that IL-4 is an inflammatory component mediating intolerance reactions to aspirin, and thus is crucial for AERD pathogenesis.
authors.affiliation: Department of Bionano Technology, Hanyang University, Ansan, Republic of Korea.
authors.forename: Su-Kang
authors.initials: SK
authors.lastname: Kong
authors.affiliation: Department of Bionano Technology, Hanyang University, Ansan, Republic of Korea.
authors.forename: Byung
authors.initials: B
authors.lastname: Soo Kim
authors.affiliation: Department of Molecular and Life Sciences, College of Science and Technology, Hanyang University, Ansan, Republic of Korea.
authors.forename: Tae
authors.initials: T
authors.lastname: Gi Uhm
authors.affiliation: Soonchunhyang Medical Science Research Institute, College of Medicine, Soonchunhyang University, 22, Soonchunhyang-ro, Asan, Chungcheongnam-do, Republic of Korea.
authors.forename: Hun
authors.initials: H
authors.lastname: Soo Chang
authors.affiliation: Division of Allergy and Respiratory, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, Republic of Korea.
authors.forename: Jong
authors.initials: J
authors.lastname: Sook Park
authors.affiliation: Division of Allergy and Respiratory, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, Republic of Korea.
authors.forename: Sung
authors.initials: S
authors.lastname: Woo Park
authors.affiliation: Division of Allergy and Respiratory, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, Republic of Korea.
authors.forename: Choon-Sik
authors.initials: CS
authors.lastname: Park
authors.affiliation: Department of Bionano Technology, Hanyang University, Ansan, Republic of Korea.|Department of Molecular and Life Sciences, College of Science and Technology, Hanyang University, Ansan, Republic of Korea.
authors.forename: Il Yup
authors.initials: IY
authors.lastname: Chung
mesh_terms: D001241:Aspirin / Q000009:adverse effects*; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D012120:Respiration Disorders / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D015847:Interleukin-4; D001241:Aspirin