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

in Journal of inflammation (London, England) by Yinying Ren, Mi Zhou, Yuehan Li, Yan Li, JinYing Xiang, Fang Deng, Zhengxiu Luo, Enmei Liu, Jinyue Yu, Zhou Fu, Fengxia Ding, Bo Liu

TLDR

  • M2Φ-Exos regulate airway inflammation in asthma by modulating epithelial cell proliferation and apoptosis, reducing inflammation and improving lung function.
  • These exosomes decreased inflammation and tissue thickening in the lungs of mice with asthma, and increased anti-inflammatory compound production.

Abstract

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. 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. 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. 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.

Overview

  • This study examines the role of M2 macrophage-derived exosomes (M2Φ-Exos) in regulating airway inflammation in asthma by modulating epithelial cell proliferation and apoptosis.
  • M2Φ-Exos were extracted and characterized, and their effects were evaluated in vitro on mouse lung epithelial cells and in vivo on asthmatic mice.
  • The study aims to understand the mechanisms by which M2Φ-Exos regulate epithelial proliferation and apoptosis, and identify potential therapeutic strategies for asthma management.

Comparative Analysis & Findings

  • M2Φ-Exos reduced abnormal proliferation and apoptosis in HDM-stimulated mouse lung epithelial cells, indicating their anti-inflammatory effects.
  • In asthmatic mice, M2Φ-Exos alleviated airway inflammation, epithelial thickening, and inflammatory cytokine production, while increasing anti-inflammatory cytokine levels.
  • M2Φ-Exos regulated the imbalance in epithelial proliferation and apoptosis, reducing PCNA, cleaved caspase-3, and Bax levels and increasing Bcl-2 expression.

Implications and Future Directions

  • These findings provide new insights into the potential therapeutic strategies for asthma management by modulating M2Φ-Exos-mediated effects on epithelial cell proliferation and apoptosis.
  • Future studies could investigate the role of M2Φ-Exos in human asthma, explore their potential use as a diagnostic biomarker, and evaluate their therapeutic efficacy in clinical trials.
  • Additionally, understanding the specific signaling pathways and mechanisms by which M2Φ-Exos regulate epithelial cell behavior could lead to the development of targeted therapies for asthma treatment.
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