Exp Mol Med.  2016 Jan;48(1):e202. 10.1038/emm.2015.96.

Aspirin induces IL-4 production: augmented IL-4 production in aspirin-exacerbated respiratory disease

• Kong SK
• Kim BS
• Uhm TG
• Chang HS
• Park JS
• Park SW
• Park CS
• Chung IY

• KMID: 2327672
• DOI: http://doi.org/10.1038/emm.2015.96

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.

MeSH Terms

Aspirin*
Asthma
Cyclooxygenase 1
Eating
Humans
Hypersensitivity
Inflammation
Interleukin-4*
Mitogen-Activated Protein Kinases
Negotiating
Respiratory System
T-Lymphocytes
Transcription Factors
Aspirin
Cyclooxygenase 1
Interleukin-4
Mitogen-Activated Protein Kinases
Transcription Factors