Aspirin induces IL-4 mRNA expression via activation of MAPKs pathway (HYP6P.272)

Abstract

Abstract Aspirin-exacerbated respiratory disease is characterized by asthma, nasal polyps, and intolerance to aspirin. IL-4 is mainly produced by allergic cells, including Th2 cells, mast cells, and eosinophils, and plays a central role in pathogenesis of allergic diseases such as asthma. In the present study, we demonstrated that aspirin induced IL-4 expression. Aspirin dose-dependently induced IL-4 mRNA and IL-4 promoter reporter activity in these three cell types. Treatment with pharmacologic inhibitors showed that the aspirin-induced IL-4 expression occurred through the MAPK ERK1/2 pathway, which was consistent with the observation that aspirin induced ERK phosphorylation. Analysis of serially deleted IL-4 promoter reporter showed that aspirin elevated the promoter activities regardless of the deleted constructs. When nuclear extract from these cells treated with aspirin were reacted with the probes harboring P0, P1, P2, P3, P4, P5 elements, and a region between P1 and P2 elements, DNA-protein complexes were remarkably augmented in the probes. Some of the DNA-protein complexes were supershifted by anti-NFAT. Collectively, these data indicate that aspirin induces IL-4 expression via ERK1/2 activation and availability of transcription factors that bind critical cis-acting elements in IL-4 promoter, thereby contributing to pathogenesis of aspirin-intolerant asthma.