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

IF 4.4 3区医学 Q2 IMMUNOLOGY

Journal of Inflammation-London Pub Date : 2025-05-19 DOI:10.1186/s12950-025-00444-y

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

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引用次数: 0

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.

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来源于M2巨噬细胞的外泌体通过调节上皮细胞的增殖和凋亡来调节气道炎症。

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巨噬细胞来源的外泌体（M2Φ-Exos）通过调节上皮细胞增殖和凋亡调节哮喘气道炎症的机制。方法：提取M2Φ-Exos，通过形态、大小、标记蛋白表达进行表征。在体外实验中，利用western blotting分析M2Φ-Exos对屋尘螨（HDM）刺激小鼠肺上皮细胞（MLE-12s）的影响，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cleaved caspase-3的表达。在体内，通过免疫组织化学、免疫荧光和免疫印迹技术，对hdm诱导的哮喘小鼠给予M2Φ-Exos，以评估其对气道炎症、上皮重塑和增殖-凋亡平衡的影响。采用qRT-PCR和ELISA检测肺组织和支气管肺泡灌洗液（BALF）中细胞因子水平。结果：M2Φ-Exos呈典型的杯状形态，平均直径115.5 nm，表达标记蛋白CD9、TSG101、CD63。MLE-12细胞内化M2Φ-Exos，导致hdm刺激细胞的异常增殖和凋亡减少。在哮喘小鼠中，M2Φ-Exos减轻气道炎症和上皮增厚，同时降低PCNA、裂解caspase-3和Bax水平，增加Bcl-2表达。M2Φ-Exos抑制促炎因子（IL-4、IL-5、IL-13）和转化生长因子(TGF)-β，增强抗炎因子IFN-γ和IL-10。结论：研究结果表明M2Φ-Exos可调节哮喘患者上皮细胞增殖和凋亡失衡，减轻炎症，减轻组织重塑，为哮喘治疗提供了新的思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Inflammation-London IMMUNOLOGY-

CiteScore

7.90

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Journal of Inflammation welcomes research submissions on all aspects of inflammation. The five classical symptoms of inflammation, namely redness (rubor), swelling (tumour), heat (calor), pain (dolor) and loss of function (functio laesa), are only part of the story. The term inflammation is taken to include the full range of underlying cellular and molecular mechanisms involved, not only in the production of the inflammatory responses but, more importantly in clinical terms, in the healing process as well. Thus the journal covers molecular, cellular, animal and clinical studies, and related aspects of pharmacology, such as anti-inflammatory drug development, trials and therapeutic developments. It also considers publication of negative findings. Journal of Inflammation aims to become the leading online journal on inflammation and, as online journals replace printed ones over the next decade, the main open access inflammation journal. Open access guarantees a larger audience, and thus impact, than any restricted access equivalent, and increasingly so, as the escalating costs of printed journals puts them outside University budgets. The unrestricted access to research findings in inflammation aids in promoting dynamic and productive dialogue between industrial and academic members of the inflammation research community, which plays such an important part in the development of future generations of anti-inflammatory therapies.