Pirfenidone inhibits the polarization of M2 macrophages by down-regulating IRF4 to reduce the occurrence and development of radiation-induced lung fibrosis
10.3760/cma.j.cn113030-20210331-00128
- VernacularTitle:吡非尼酮下调IRF4抑制M2型巨噬细胞活化减轻放射性肺纤维化机制
- Author:
Min FANG
1
;
Hangjie YING
;
Qingqing HANG
;
Yamei CHEN
;
Ming CHEN
Author Information
1. 中国科学院大学附属肿瘤医院（浙江省肿瘤医院）放疗科，中国科学院基础医学与肿瘤研究所，杭州 310022
- Keywords:
Pirfenidone;
Radiation-induced lung fibrosis;
Macrophage;
Interferon regulatory factor 4
- From:
Chinese Journal of Radiation Oncology
2022;31(6):562-568
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the preventive and therapeutic effect of pirfenidone (PFD) on radiation-induced lung fibrosis (RILF) and its mechanism.Methods:40 female C57/BL6 mice were randomly divided into 4 groups: negative control group (NC), PFD treatment group (PFD), radiation treatment group (RT) and radiation plus PFD treatment group (RT+ PFD). Mice in RT and RT+ PFD groups received a single whole lung X-ray consisting of a 50 Gy dose of radiation, delivered by small animal radiation research platform (SARRP). PFD at a dose of 300 mg/kg was administered orally 2 h before irradiation for 150 d. HE and Masson staining were used to detect the infiltration of inflammatory cells and the degree of pulmonary fibrosis. Quantitative real-time PCR (qPCR) and Western blotting (WB) were adopted to detect the expression levels of M1/M2 macrophage phenotypic markers. The expression levels of arginase-1(ARG-1), chitinase 3-like protein 3(YM-1) and interferon regulatory factor-4(IRF4) of macrophages stimulated with IL-4 and IL-13 were detected by WB. In addition, immunofluorescence staining was used to detect the expression and translocation of IRF4 in macrophages among different treatment groups.Results:HE and Masson staining showed that PFD could significantly inhibit radiation-induced infiltration of inflammatory cells and fibrosis in lung tissues. The M2 macrophages and expression levels of ARG-1 and YM-1 were down-regulated in the RT+ PFD group. Cell experiments further confirmed that PFD could significantly inhibit the polarization of macrophages to M2 induced by IL-4+ IL-13, which was mainly related to the down-regulation of IRF4.Conclusion:PFD has a preventive and therapeutic effect on RILF by inhibiting IRF4 and reducing the polarization of macrophages to M2.
