Regulation of IL-4 expression by aspirin via a MAPK pathway

Abstract

IL-4, a pleiotropic cytokine produced in Th2 cells, plays a central role in the pathological development of asthma. Aspirin, a widely used nonsteroidal anti-inflammatory drug (NSAID), is reported to have inhibitory effect on IL-4 expression in activated T cells and paradoxically to induce airway hyperreactivity in a subset of asthmatic patients, causing so-called aspirin-intolerant asthma (AIA) by completely unknown mechanism. Here we show the effects of aspirin on IL-4 expression in Jurkat T cells and K562 cells that are shown to be able to express IL-4 mRNA. qPCR analysis revealed that aspirin induced IL-4 mRNA expression in both cell lines. In agreement, aspirin also transactivated IL-4 promoter. Analysis of IL-4 promoter deletion constructs showed that the asprin-mediated IL-4 induction was not attributable to any discrete motif in the IL-4 promoter: all the deletion constructs exhibited the increased reporter activities in response to aspirin. Aspirin was able to activate p38 and ERK1/2, and specific inhibitors for these kinases abolished aspirin-mediated IL-4 induction and IL-4 promoter activity. Aspirin-induced IL-4 expression might implicate airway hyperreactivity found in AIA.