Interleukin-37 alleviates airway inflammation and remodeling in asthma via inhibiting the activation of NF-κB and STAT3 signalings

Asthma is a common respiratory inflammatory disorder disease of childhood, and airway smooth muscle cells (ASMCs) play an important role in this disease. Recently, studies have found that interleukin (IL)-37 inhibits allergic airway inflammation of asthmatic mouse models. The aim of this study was to investigate the exact mechanism of IL-37 in asthma. In this study, we found recombinant human IL-37 protein significantly reduced ovalbumin (OVA)-induced airway hyperresponsiveness, inflammatory cell infiltration, the epithelial-mesenchymal-transition (EMT) process, and levels of IL-4, IL-6 and IL-13, but increased interferon (IFN)-γ expression. Moreover, IL-37 treatment remarkably inhibited transforming growth factor (TGF)-β1-induced cell proliferation, migration, EMT, and inflammatory response in ASMCs. IL-37 notably upregulated IκB expression and downregulated levels of NF-κB p65, phospho-NF-κB p65, STAT3 and phospho-STAT3 both in OVA-induced mice and in TGF-β1-stimulated ASMCs. The effects of IL-37 on TGF-β1-induced ASMCs were abrogated by STAT3 upregulation. Additionally, PDTC, a NF-κB inhibitor, showed the similar effects as IL-37 in ASMCs. In conclusion, IL-37 may alleviate airway inflammation and remodeling in asthma through suppressing the activation of NF-κB and STAT3. •IL-37 attenuates asthmatic symptoms and Th1/Th2 imbalance in OVA-induced mice.•IL-37 suppresses EMT process, and NF-κB and STAT3 signalings in allergic mice.•IL-37 inhibits the proliferation, migration, EMT, and inflammation in ASMCs.•IL-37 functions via the inactivation of NF-κB and STAT3 in TGF-β1-induced ASMCs.