Abstract
Asthma is a chronic respiratory disease with high heterogeneity in human. Different mouse models have been applied for investigation of pathogenesis and treatment of asthma, which target on different cells, receptors and pathways. Interleukin (IL-) 28B, a member of λ-interferons, have been shown to play a protective role in OVA-induced asthma, which is antigen-specific and adaptive immune system dominant. However, the roles of IL-28B in protease-induced asthma, an adaptive immune system independent asthma, are still unclear. Here, we used plant-derived cysteine protease, papain to induce asthma in mice and found that IL-28B was capable of alleviating papain-induced asthma. Papain challenge lead to activation of epithelial cells and production of alarmin, such as IL-25 and thymic stromal lymphopoietin and IL-28B treatment down-regulated their production. Further mechanism was proved to be that IL-28B inhibited the phosphorylation of Erk in epithelial cells via interaction with their receptors. Our results reveal a protective role of IL-28B via regulation of epithelial cells in protease induced asthma.
Highlights
Asthma is a chronic pulmonary disease characterized by airway hyper-responsiveness (AHR), inflammatory immune response, mucus overproduction, airway remodeling and airflow limitation
IL-28A, IL-28B and IL-29 share a unique heterodimeric receptor IFNLR consisting of IL-28Rα and IL-10R, which is mainly expressed by epithelial cells, dendritic cells (DCs) and m acrophages[8,9,10]
The results showed that the frequency and number of neutrophils (CD45+CD11b+Ly6G+) were reduced in pliveIL-28B treated mice compared with plive-vector or PBS treated mice (Fig. 2D–F)
Summary
Asthma is a chronic pulmonary disease characterized by airway hyper-responsiveness (AHR), inflammatory immune response, mucus overproduction, airway remodeling and airflow limitation. Plant-derived cysteine protease, papain induces asthma in mice initiated by activation of protease-activated receptor (PAR) signaling pathway and the subsequent production of IL-33, IL-25 and thymic stromal lymphopoietin (TSLP) from airway epithelial cells, followed by secretion of IL-5 and IL-13 by lung group 2 innate lymphoid cells (ILC2s)[3,6]. Different from OVA/alum induced asthma, papain can induce asthma in the absence of adaptive immune system, which resemble an “innate-like” asthma Other models such as HDM, an animal-derived counterpart of papain, and Alternaria althernata have been applied[7]. The results revealed that IL-28B regulates IL-25 and TSLP expression in epithelial cells via Erk signaling pathway. These data suggested that IL-28B dampens protease-induced lung inflammation, mainly via inhibition of IL-25 and TSLP in epithelial cells
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