源自M2巨噬细胞的外泌体通过调节上皮细胞增殖和凋亡来调控气道炎症。

Exosomes derived from M2 macrophages regulate airway inflammation by modulating epithelial cell proliferation and apoptosis.

作者信息

Ren Yinying, Zhou Mi, Li Yuehan, Li Yan, Xiang JinYing, Deng Fang, Luo Zhengxiu, Liu Enmei, Yu Jinyue, Fu Zhou, Ding Fengxia, Liu Bo

机构信息

Department of Respiratory Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Engineering Research Center of Stem Cell Therapy, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong Dis, Chongqing, 400014, China.

Bristol Medical School, University of Bristol, Bristol, UK.

出版信息

J Inflamm (Lond). 2025 May 19;22(1):19. doi: 10.1186/s12950-025-00444-y.

DOI:10.1186/s12950-025-00444-y

PMID:40390011

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12090695/

Abstract

BACKGROUND

Asthma is a chronic inflammatory disease characterized by airway remodeling and immune dysregulation. This study aimed to explore the mechanisms by which M2 macrophage-derived exosomes (M2Φ-Exos) regulate airway inflammation in asthma by modulating epithelial cell proliferation and apoptosis.

METHODS

M2Φ-Exos were extracted and characterized by morphology, size, and marker protein expression. In vitro, the effects of M2Φ-Exos on House Dust Mites (HDM)-stimulated mouse lung epithelial cells (MLE-12s) were evaluated using western blotting to analyze Proliferating Cell Nuclear Antigen (PCNA), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved caspase-3 expression. In vivo, M2Φ-Exos were administered to HDM-induced asthmatic mice to assess their impact on airway inflammation, epithelial remodeling, and proliferation-apoptosis balance using immunohistochemistry, immunofluorescence, and western blotting. Cytokine levels in lung tissue and bronchoalveolar lavage fluid (BALF) were measured by qRT-PCR and ELISA.

RESULTS

M2Φ-Exos displayed typical cup-shaped morphology, an average diameter of 115.5 nm, and expressed marker proteins CD9, TSG101, and CD63. MLE-12 cells internalized M2Φ-Exos, leading to reduced abnormal proliferation and apoptosis in HDM-stimulated cells. In asthmatic mice, M2Φ-Exos alleviated airway inflammation and epithelial thickening while reducing PCNA, cleaved caspase-3, and Bax levels and increasing Bcl-2 expression. M2Φ-Exos suppressed pro-inflammatory cytokines (IL-4, IL-5, IL-13) and Transforming growth factor (TGF)-β, while enhancing anti-inflammatory cytokine IFN-γ and IL-10.

CONCLUSION

These findings demonstrate that M2Φ-Exos regulate the imbalance in epithelial proliferation and apoptosis in asthma, reducing inflammation and mitigating tissue remodeling, and provide new insights into potential therapeutic strategies for asthma management.

摘要

背景

哮喘是一种以气道重塑和免疫失调为特征的慢性炎症性疾病。本研究旨在探讨M2巨噬细胞衍生外泌体（M2Φ-Exos）通过调节上皮细胞增殖和凋亡来调控哮喘气道炎症的机制。

方法

提取M2Φ-Exos并通过形态、大小和标志物蛋白表达进行表征。在体外，使用蛋白质免疫印迹法分析增殖细胞核抗原（PCNA）、B细胞淋巴瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）和裂解的半胱天冬酶-3表达，评估M2Φ-Exos对屋尘螨（HDM）刺激的小鼠肺上皮细胞（MLE-12s）的影响。在体内，将M2Φ-Exos给予HDM诱导的哮喘小鼠，使用免疫组织化学、免疫荧光和蛋白质免疫印迹法评估其对气道炎症、上皮重塑和增殖-凋亡平衡的影响。通过qRT-PCR和ELISA测量肺组织和支气管肺泡灌洗液（BALF）中的细胞因子水平。

结果

M2Φ-Exos呈现典型的杯状形态，平均直径为115.5nm，并表达标志物蛋白CD9、TSG101和CD63。MLE-12细胞摄取M2Φ-Exos，导致HDM刺激的细胞中异常增殖和凋亡减少。在哮喘小鼠中，M2Φ-Exos减轻了气道炎症和上皮增厚，同时降低了PCNA、裂解的半胱天冬酶-3和Bax水平，并增加了Bcl-2表达。M2Φ-Exos抑制促炎细胞因子（IL-4、IL-5、IL-13）和转化生长因子（TGF）-β，同时增强抗炎细胞因子IFN-γ和IL-10。