IL‑27 suppresses airway inflammation, hyperresponsiveness and remodeling via the STAT1 and STAT3 pathways in mice with allergic asthma.

Abstract

Type 2 cytokine-associated immunity may be involved in the pathogenesis of allergic asthma. Although interleukin 27 (IL-27) has been reported as an initiator and suppressor of T-helper 1 (Th1) and T-helper 2 (Th2) responses, respectively, its effects on the development of asthma remain unclear. In the present study, mice were induced and challenged with ovalbumin and received subsequent intranasal administration of IL-27. Total and differential cell counts were determined from Wright-Giemsa-stained cytospins, whereas the cytokine levels were detected using ELISA. In addition, the expression levels of signal transducer and activator of transcription (STAT) 1, STAT3, GATA-binding protein-3 (GATA3) and T-bet (T-box transcription factor) were analyzed in T cells by western blot analysis. Their corresponding mRNA expression levels were determined by quantitative PCR. Airway remodeling was assessed by conventional pathological techniques. The results indicated that intranasal administration of IL-27 ameliorated airway inflammation and hyperresponsiveness in an acute model of asthma. Furthermore, IL-27 prevented airway remodeling in a chronic model of asthma. Following administration of IL-27, the mRNA expression levels of STAT1 and T-bet were upregulated, while those of GATA3 were downregulated. Moreover, the phosphorylation levels of STAT1 and STAT3 were increased. Taken together, these findings demonstrated that intranasal administration of IL-27 ameliorated Th2-related allergic lung inflammation and remodeling in mouse models of asthma by repairing both the STAT1 and STAT3 pathways.