PPAR? inhibits small airway remodeling through mediating the polarization homeostasis of alveolar macrophages in COPD

作者全名："He, Sirong; Tian, Ruoyuan; Zhang, Xinying; Yao, Qingmei; Chen, Quan; Liu, Bicui; Liao, Lele; Gong, Yuxuan; Yang, Hua; Wang, Dan"

作者地址："[He, Sirong; Tian, Ruoyuan; Zhang, Xinying; Yao, Qingmei; Wang, Dan] Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [He, Sirong; Tian, Ruoyuan; Zhang, Xinying; Chen, Quan] Chongqing Med Univ, Coll Basic Med, Dept Immunol, Chongqing 400016, Peoples R China; [Liu, Bicui] Bishan Hosp Chongqing, Dept Resp & Crit Care Med, Chongqing 404000, Peoples R China; [Liao, Lele] Second Hosp Jiulongpo Dist, Dept Resp Med, Chongqing 400050, Peoples R China; [Gong, Yuxuan] Chongqing Med Univ, Int Med Coll, Chongqing 401334, Peoples R China; [Yang, Hua] Hubei Minzu Univ, Minda Hosp, Resp Dept, Enshi 445000, Peoples R China"

通信作者："Wang, D (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：CLINICAL IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000966406900001

JCR分区：Q1

影响因子：8.6

年份：2023

卷号：250

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：PPAR?; Alveolar macrophages; Polarization homeostasis; Airway remodeling; COPD

摘要："The role of Peroxisome Proliferator-Activated Receptor-gamma (PPAR gamma) in alveolar macrophages(AMs) polarization homeostasis is closely associated with airway remodeling in COPD, but the definite mechanism remains unclear. In this study, elevated percentage of M1-type AMs and the expression of functionally cytokines were found in COPD patients and mice, which closely related to the disease severity. PPAR gamma was markedly up-regulated in M2-type AMs and down-regulated in M1-type AMs, and was associated with disease severity in COPD. Co-cultured with M1-or M2-type AMs promoted the epithelial-mesenchymal transition (EMT) of airway epithelial cells and the proliferation of airway smooth muscle cells. Moreover, airway remodeling and functional damage were observed in both IL4R-/-COPD mice with runaway M1-type AMs polarization and TLR4-/-COPD mice with runaway M2-type AMs polarization. Cigarette extract (CS) or lipopolysaccharide (LPS) stimulated PPAR gamma-/-AMs showed more serious polarization disorder towards M1, as well as CS induced PPAR gamma- /-COPD mice, which led to more severe airway inflammation, lung function damage, and airway remodeling. Treatment with PPAR gamma agonist significantly improved the polarization disorder and function activity in CS/LPS stimulated-AMs by inhibiting the JAK-STAT, MAPK and NF-kappa B pathways, and alleviated the airway inflammation, restored the lung function and suppressed airway remodeling in CS induced-COPD mice. Our research demonstrates that polari-zation homeostasis of AMs mediated by PPAR gamma has the protective effect in airway remodeling, and may be a novel therapeutic target for the intervention and treatment of airway remodeling in COPD."

基金机构："Program of National Natural Science Foundation of China [82000026]; Natural Science Foundation of Chongqing, China [cstc2021jcyj-msxmX0151]; Key project of Scientific Research Plan of Hubei Education Department [D20191902]; Cultivation Fund of The First Affiliated Hospital of Chongqing Medical University, China [PYJJ2020-03]; CQMU Program for Youth Innovation in Future Medicine [W0100]; Postdoctoral Cultivation Fund of The First Affiliated Hospital of Chongqing Medical University, China [CYYY-BSHPYXM-202215]"

基金资助正文："This work was sponsored by the Program of National Natural Science Foundation of China (No.82000026) , Natural Science Foundation of Chongqing, China (No. cstc2021jcyj-msxmX0151) , Key project of Scientific Research Plan of Hubei Education Department (D20191902) , Cultivation Fund of The First Affiliated Hospital of Chongqing Medical University, China (No.PYJJ2020-03) , The CQMU Program for Youth Innovation in Future Medicine (No.W0100) and Postdoctoral Cultivation Fund of The First Affiliated Hospital of Chongqing Medical University, China (No.CYYY-BSHPYXM-202215) ."