%0 Journal Article
%T Feature Article: IL
%A Biyun Li
%A Huaping Dai
%A Jinglan Zhang
%A Sa Luo
%A Xuefeng Xu
%J Experimental Biology and Medicine
%@ 1535-3699
%D 2019
%R 10.1177/1535370219843827
%X Interleukin (IL)-25 is shown to potentiate type-2 immunity and contribute to chronic airway inflammation and remodeling in allergic airway diseases. However, the role of IL-25 in idiopathic pulmonary fibrosis (IPF), dominated by nonatopic type-2 immunity, still remains largely unclear. Herein, we detected the expression levels of IL-25 and IL-17BR (IL-25¡¯s receptor) by using lung tissue samples gained from IPF patients and normal subjects. Also, by directly intranasal (IN) instillation of IL-25 to mice, we examined the potential roles and mechanisms of IL-25 in the development of lung fibrosis. Furthermore, we tested whether IL-25 can directly activate human lung fibroblast by in vitro cell culture. Immunohistochemical, Western blot, and real-time reverse transcription-polymerase chain reaction (RT-PCR) showed that the mRNA and protein levels of IL-25 and IL-17BR are significantly higher in IPF patients when compared with normal controls. Intranasal instillation of IL-25 to mice markedly induces the expressions of alveolar IL-5 and IL-13. Furthermore, immunohistochemical analysis showed that the main components of the extracellular matrix including collagen I, collagen III and fibronectin are notably induced by IL-25 instillation in lung parenchyma (especially in alveolar epithelial cells [AECs]). Also, IL-25 potentiates the expression of connective tissue growth factor (CTGF) in AECs and the recruitment of lung fibroblast. By using Cell Counting Kit-8 and EDU incorporation assay, we found that IL-25 markedly enhances the proliferation of lung fibroblast. Finally, IL-25 potentiates fibroblast to produce several fibrogenic genes including collagen I/III, fibronectin, CTGF, ¦Á smooth muscle (¦Á-SMA) and tissue inhibitor of metalloproteinase (TIMP)-1 as determined by RT-PCR assay. Collectively, we concluded that IL-25 is increased in IPF lungs and contributes to lung fibrosis by directly mediating AECs/fibroblast activation. Our work focused on alveolar epithelial cells (AECs)-derived type-2 cytokine (interleukin [IL]-25) in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We showed that IL-25 and IL-17BR (IL-25¡¯s receptor) is upregulated in lung tissues (especially in AECs and lung fibroblasts) of IPF patients and contributes to lung fibrosis by directly activating lung fibroblasts and modulating epithelial¨Cmesenchymal transition (EMT) of AECs. We suggest that IL-25 may be one of the master switches hidden in the milieu of abnormal epithelial¨Cmesenchymal crosstalk. Treatment targeting IL-25 may be the potential and novel method for IPF patients
%K Alveolar epithelial cells
%K fibroblasts
%K interleukin-25
%K lung fibrosis
%K murine model
%U https://journals.sagepub.com/doi/full/10.1177/1535370219843827