IL33/ST2 contributes to airway remodeling via p-JNK MAPK/STAT3 signaling pathway in OVA-induced allergic airway inflammation in mice

Abstract

Aim of this study: Airway remodeling, which encompasses structural changes in airway is a main feature of asthma. Interleukin-33 (IL-33) has been reported to be a vital cytokine in airway remodeling in asthma, but the underlying mechanisms are not clear yet. This study focused on discussing the role of IL-33 in airway remodeling in asthma. Material and methods: Female BALB/c mice were divided into a control group, an OVA induced allergic airway disease group and an anti-ST2 antibody intervention group. Immunohistochemistry and western blot were performed to detect IL-33, ST2 expression in addition to airway remodeling markers a-smooth muscle actin (a-SMA) and type 1 collagen in OVA-induced mice model. Levels of p-JNK and p-STAT3 activation in mice were detected by western blot. Human lung fibroblast (HLF) were stimulated with rhIL-33, anti-ST2 antibody and JNK inhibitor sp600125 and levels of JNK and STAT3 activation were determined via western blot and immunofluorescence staining. Results: Anti-ST2 treatment inhibited JNK/STAT3 phosphorylation and airway remodeling in OVA-induced mouse model. IL-33 induced a-SMA and collagen 1 expression was inhibited by anti-ST2 antibody and sp600125 treatment via decreased JNK/STAT3 phosphorylation in human lung fibroblast. Conclusions: IL-33 promoted airway remodeling by interacting with ST2 to activate the JNK/STAT3 signaling pathway in asthma.