Aspirin induces IL-4 production: augmented IL-4 production in aspirin-exacerbated respiratory disease.
- Author:
Su Kang KONG
1
;
Byung Soo KIM
;
Tae Gi UHM
;
Hun Soo CHANG
;
Jong Sook PARK
;
Sung Woo PARK
;
Choon Sik PARK
;
Il Yup CHUNG
Author Information
- Publication Type:Original Article
- MeSH: Aspirin*; Asthma; Cyclooxygenase 1; Eating; Humans; Hypersensitivity; Inflammation; Interleukin-4*; Mitogen-Activated Protein Kinases; Negotiating; Respiratory System; T-Lymphocytes; Transcription Factors
- From:Experimental & Molecular Medicine 2016;48(1):e202-
- CountryRepublic of Korea
- Language:English
- 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.
