Cigarette Smoke-induced Exosomal MiR-221-3p Facilitates M1 Macrophage Polarization Via the STAT3 Pathway in Chronic Obstructive Pulmonary Disease

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2024 Aug 30

PMID 39213192

Authors

Hui Jia

Wei He

Bo Wu

Zhaoshuang Zhong

Yuele Chang

Yang Liu

Min Wang

Shuyue Xia

Affiliations

Soon will be listed here.

Abstract

Aims: Chronic obstructive pulmonary disease (COPD) is marked by irreversible airflow limitations stemming from small airway constriction and lung emphysema. The advancement of COPD is greatly influenced by the M1 polarization of macrophages. The mechanisms governing macrophage polarization in inflammation conditions in COPD are not yet fully understood.

Methods: To investigate the interplay between exosomes triggered by cigarette smoke and the polarization of macrophages, we utilized a combination of flow cytometry, quantitative real-time reverse transcription PCR, and western blot analysis.

Results: Our research reveals that cigarette smoke (CS) exposure induces the secretion of exosomes from human bronchial epithelial cells, with exosomal miR-221-3p identified as a key player in modulating the polarization of M1 macrophages. The evidence indicates that cigarette smoke promotes exosome secretion in these cells, with exosomal miR-221-3p targeting SOCS3 and regulating the STAT3 signaling pathway to facilitate M1 macrophage polarization.

Conclusions: This research delves into the molecular pathways through which miR-221-3p facilitates the polarization of M1 macrophages, presenting a groundbreaking approach for potential targeted therapy in COPD.

References

Chen Z, Wu H, Fan W, Zhang J, Yao Y, Su W . Naringenin suppresses BEAS-2B-derived extracellular vesicular cargoes disorder caused by cigarette smoke extract thereby inhibiting M1 macrophage polarization. Front Immunol. 2022; 13:930476. PMC: 9342665. DOI: 10.3389/fimmu.2022.930476. View

Jiang J, Zhang S, Shen H, Guan Y, Liu Q, Zhao W . Rac1 signaling regulates cigarette smoke-induced inflammation in the lung via the Erk1/2 MAPK and STAT3 pathways. Biochim Biophys Acta Mol Basis Dis. 2017; 1863(7):1778-1788. DOI: 10.1016/j.bbadis.2017.04.013. View

Wang L, Chen Q, Yu Q, Xiao J, Zhao H . Cigarette smoke extract-treated airway epithelial cells-derived exosomes promote M1 macrophage polarization in chronic obstructive pulmonary disease. Int Immunopharmacol. 2021; 96:107700. DOI: 10.1016/j.intimp.2021.107700. View

Liu W, Lin H, Nie W, Wan J, Jiang Q, Zhang A . Exosomal miR-221-3p Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Asthma Progression by Targeting FGF2 and Inhibiting the ERK1/2 Signaling Pathway. Evid Based Complement Alternat Med. 2022; 2022:5910874. PMC: 9385294. DOI: 10.1155/2022/5910874. View

Zhang J, Zhou X, Hao H . Macrophage phenotype-switching in cancer. Eur J Pharmacol. 2022; 931:175229. DOI: 10.1016/j.ejphar.2022.175229. View

Zhou C, Ma J, Huang L, Yi H, Zhang Y, Wu X . Cervical squamous cell carcinoma-secreted exosomal miR-221-3p promotes lymphangiogenesis and lymphatic metastasis by targeting VASH1. Oncogene. 2018; 38(8):1256-1268. PMC: 6363643. DOI: 10.1038/s41388-018-0511-x. View

Coronel-Hernandez J, Delgado-Waldo I, Cantu de Leon D, Lopez-Camarillo C, Jacobo-Herrera N, Ramos-Payan R . HypoxaMIRs: Key Regulators of Hallmarks of Colorectal Cancer. Cells. 2022; 11(12). PMC: 9221210. DOI: 10.3390/cells11121895. View

Rayamajhi S, Nguyen T, Marasini R, Aryal S . Macrophage-derived exosome-mimetic hybrid vesicles for tumor targeted drug delivery. Acta Biomater. 2019; 94:482-494. DOI: 10.1016/j.actbio.2019.05.054. View

He C, Zheng S, Luo Y, Wang B . Exosome Theranostics: Biology and Translational Medicine. Theranostics. 2018; 8(1):237-255. PMC: 5743472. DOI: 10.7150/thno.21945. View

10.

Wang L, Zhang S, Wu H, Rong X, Guo J . M2b macrophage polarization and its roles in diseases. J Leukoc Biol. 2018; 106(2):345-358. PMC: 7379745. DOI: 10.1002/JLB.3RU1018-378RR. View

11.

Negewo N, Gibson P, McDonald V . COPD and its comorbidities: Impact, measurement and mechanisms. Respirology. 2015; 20(8):1160-71. DOI: 10.1111/resp.12642. View

12.

Zhu Z, Lian X, Su X, Wu W, Zeng Y, Chen X . Exosomes derived from adipose-derived stem cells alleviate cigarette smoke-induced lung inflammation and injury by inhibiting alveolar macrophages pyroptosis. Respir Res. 2022; 23(1):5. PMC: 8753876. DOI: 10.1186/s12931-022-01926-w. View

13.

Liu C, Yao Z, Wang J, Zhang W, Yang Y, Zhang Y . Macrophage-derived CCL5 facilitates immune escape of colorectal cancer cells via the p65/STAT3-CSN5-PD-L1 pathway. Cell Death Differ. 2019; 27(6):1765-1781. PMC: 7244707. DOI: 10.1038/s41418-019-0460-0. View

14.

Kumar A, Deep G . Hypoxia in tumor microenvironment regulates exosome biogenesis: Molecular mechanisms and translational opportunities. Cancer Lett. 2020; 479:23-30. DOI: 10.1016/j.canlet.2020.03.017. View

15.

Poulet C, Njock M, Moermans C, Louis E, Louis R, Malaise M . Exosomal Long Non-Coding RNAs in Lung Diseases. Int J Mol Sci. 2020; 21(10). PMC: 7279016. DOI: 10.3390/ijms21103580. View

16.

Liu T, Zhang Z, Shen W, Wu Y, Bian T . MicroRNA Let-7 Induces M2 Macrophage Polarization in COPD Emphysema Through the IL-6/STAT3 Pathway. Int J Chron Obstruct Pulmon Dis. 2023; 18:575-591. PMC: 10108876. DOI: 10.2147/COPD.S404850. View

17.

Lee H, Abston E, Zhang D, Rai A, Jin Y . Extracellular Vesicle: An Emerging Mediator of Intercellular Crosstalk in Lung Inflammation and Injury. Front Immunol. 2018; 9:924. PMC: 5946167. DOI: 10.3389/fimmu.2018.00924. View

18.

Anderson N, Minutolo N, Gill S, Klichinsky M . Macrophage-Based Approaches for Cancer Immunotherapy. Cancer Res. 2020; 81(5):1201-1208. DOI: 10.1158/0008-5472.CAN-20-2990. View

19.

Yamada M . Extracellular vesicles: Their emerging roles in the pathogenesis of respiratory diseases. Respir Investig. 2021; 59(3):302-311. DOI: 10.1016/j.resinv.2021.02.006. View

20.

Xu Z, Zeng S, Gong Z, Yan Y . Exosome-based immunotherapy: a promising approach for cancer treatment. Mol Cancer. 2020; 19(1):160. PMC: 7661275. DOI: 10.1186/s12943-020-01278-3. View