Feature Article: IL-25 contributes to lung fibrosis by directly acting on alveolar epithelial cells and fibroblasts

被引:36
作者
Xu, Xuefeng [1 ]
Luo, Sa [2 ,3 ]
Li, Biyun [2 ,3 ]
Dai, Huaping [2 ,3 ]
Zhang, Jinglan [1 ]
机构
[1] Capital Med Univ, Beijing An Zhen Hosp, Dept Surg Intens Care Unit, Beijing 100029, Peoples R China
[2] China Japan Friendship Hosp, Natl Clin Res Ctr Resp Dis, Dept Pulm & Crit Care Med, Ctr Resp Med, Beijing 100029, Peoples R China
[3] Natl Clin Res Ctr Resp Dis, Beijing 100029, Peoples R China
基金
中国国家自然科学基金;
关键词
Alveolar epithelial cells; fibroblasts; interleukin-25; lung fibrosis; murine model; IDIOPATHIC PULMONARY-FIBROSIS; INFLAMMATION; CYTOKINES; MODEL; MICE;
D O I
10.1177/1535370219843827
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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, a smooth muscle (a-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.
引用
收藏
页码:770 / 780
页数:11
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