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

• Published in: Experimental & molecular medicine pp. 1 - 10
• Main Authors: 공수강, 김병수, Tae Gi Uhm, 장헌수, 박종숙, 박성우, 박춘식, 정일엽
• Format: Journal Article
• Language: English
• Published: 생화학분자생물학회 01.01.2016
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

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 mitogenactivated 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. KCI Citation Count: 10