Open AccessMacrophage‐derived exosomes mediate silica‐induced pulmonary fibrosis by activating fibroblast in an endoplasmic reticulum stress‐dependent manner
Author(s) -
Qin Xiaofeng,
Lin Xiaofang,
Liu Lang,
Li Ying,
Li Xiang,
Deng Zhenghao,
Chen Huiping,
Chen Hui,
Niu Zhiyuan,
Li Zisheng,
Hu Yongbin
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16524
Subject(s) - endoplasmic reticulum , proinflammatory cytokine , pulmonary fibrosis , bronchoalveolar lavage , unfolded protein response , macrophage , microvesicles , alveolar macrophage , fibrosis , fibroblast , in vivo , silicosis , inflammation , exosome , biology , tumor necrosis factor alpha , secretion , microbiology and biotechnology , chemistry , immunology , lung , medicine , in vitro , pathology , microrna , endocrinology , biochemistry , gene
Abstract Macrophages play a key role in silicosis, and exosomes are potent mediators of intercellular communication. This suggests that macrophage‐derived exosomes have a potential contribution to the pathogenesis of silicosis. To investigate whether macrophage‐derived exosomes promote or inhibit lung fibrosis, in vitro, silica‐exposed macrophage‐derived exosomes (SiO 2 ‐Exos) were collected and cocultured with fibroblasts. The expression of collagen I and α‐SMA was evaluated. Furthermore, the endoplasmic reticulum (ER) stress markers BIP, XBP1s and P ‐eIF2α were assessed after treatment with or without the ER stress inhibitor 4‐PBA. In vivo, mice were pre‐treated with the exosome secretion inhibitor GW4869 prior to silica exposure. After sacrifice, lung tissues were histologically examined, and the expression of proinflammatory cytokines (TNF‐α, IL‐1β and IL‐6) in bronchoalveolar lavage fluid (BALF) was measured. The results showed that the expression of collagen I and α‐SMA was up‐regulated after treatment with SiO 2 ‐Exos, accompanied by increased expression of BIP, XBP1s and P ‐eIF2α. Pre‐treatment with 4‐PBA reversed this effect. More importantly, an in vivo study demonstrated that pre‐treatment with GW4869 decreased lung fibrosis and the expression of TNF‐α, IL‐1β and IL‐6 in BALF. These results suggested that SiO 2 ‐Exos are profibrogenic and that the facilitating effect is dependent on ER stress.