IL-36 participated in airway remodeling in chronic asthma model by inducing epithelial-mesenchymal transition process.

Abstract

PURPOSE: Epithelial-mesenchymal transition (EMT) is a major pathological characteristic of airway remodelling in severe asthma. Interleukin (IL)-36 belongs to the IL-1 family and is associated with allergic disease, but the role of IL-36 in airway remodelling in asthma remains unclear. We aimed to explore the effect of IL-36 on EMT and to verify whether blocking IL-36-induced EMT can alleviate the airway remodeling in severe asthma. METHODS: In this study, BEAS-2B cells were stimulated with IL-36 receptor (IL-36R) agonist. The expression of epithelial‒mesenchymal transition (EMT) markers and the migration capacity of cells were determined. A chronic asthma mouse model was established to evaluate the effects of IL-36 signalling on airway inflammation and remodelling. RESULTS: In vitro, EMT and cell migration in BEAS-2B cells were induced by IL-36. In addition, IL-36 facilitated the phosphorylation of NF-κB and STAT3. In vivo, blocking IL-36R via treatment with an IL-36 receptor antagonist (IL-36Ra) inhibited the infiltration of inflammatory cells, decreased airway hyper-responsiveness (AHR) and alleviated airway remodelling (by inhibiting processes, such as EMT) in asthmatic mice. Compared with the administration of IL-36Ra alone, the coadministration of IL-36R agonist with IL-36Ra restored pathological changes related to airway remodelling. CONCLUSIONS: These data indicated that IL-36 signalling may participate in airway remodelling by inducing EMT. IL-36 may be a new therapeutic target for airway remodelling in severe asthma.