دورية أكاديمية
أعرض في EDS

Exosome microRNA-125a-5p derived from epithelium promotes M1 macrophage polarization by targeting IL1RN in chronic obstructive pulmonary disease.

التفاصيل البيبلوغرافية
العنوان: Exosome microRNA-125a-5p derived from epithelium promotes M1 macrophage polarization by targeting IL1RN in chronic obstructive pulmonary disease.
المؤلفون: Wang R; Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Taiyuan, Shanxi, China. Electronic address: wry0526@163.com., Zhu Z; Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Taiyuan, Shanxi, China., Peng S; Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Taiyuan, Shanxi, China., Xu J; Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China., Chen Y; Department of Pulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, China., Wei S; Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; Department of Pulmonary and Critical Care Medicine,Tongji Hospital,Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China., Liu X; Department of Pulmonary and Critical Care Medicine, Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; Department of Pulmonary and Critical Care Medicine,Tongji Hospital,Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Electronic address: doctorliu69@126.com.
المصدر: International immunopharmacology [Int Immunopharmacol] 2024 Aug 20; Vol. 137, pp. 112466. Date of Electronic Publication: 2024 Jun 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Science Country of Publication: Netherlands NLM ID: 100965259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-1705 (Electronic) Linking ISSN: 15675769 NLM ISO Abbreviation: Int Immunopharmacol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam ; New York : Elsevier Science, c2001-
مواضيع طبية MeSH: Exosomes*/metabolism , Interleukin 1 Receptor Antagonist Protein*/metabolism , Interleukin 1 Receptor Antagonist Protein*/genetics , Macrophages*/immunology , Macrophages*/metabolism , MicroRNAs*/metabolism , MicroRNAs*/genetics , Pulmonary Disease, Chronic Obstructive*/metabolism , Pulmonary Disease, Chronic Obstructive*/immunology, Animals ; Humans ; Male ; Mice ; Epithelial Cells/metabolism ; Macrophage Activation ; Mice, Inbred C57BL ; Respiratory Mucosa/metabolism ; Respiratory Mucosa/immunology ; Respiratory Mucosa/pathology ; THP-1 Cells
مستخلص: Background: The interplay between airway epithelium and macrophages plays a pivotal role in Chronic Obstructive Pulmonary Disease (COPD) pathogenesis. Exosomes, which transport miRNA cargo, have emerged as novel mediators of intercellular communication. MicroRNA-125a-5p (miR-125a-5p) has been implicated in macrophage polarization.This study aims to investigate the role of exosomal miR-125a-5p in the dysfunctional epithelium-macrophage cross-talk in cigarette smoke (CS)-induced COPD.
Methods: In cell models, THP-1 monocytic cells were differentiated into macrophages (M0). Human bronchial epithelial cells treated with CS extract (CSE) were co-cultured with M0. Exosomes were isolated from culture media using commercial kits and characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Exosomes labeled with PKH26 red fluorescent cell linker kits were incubated with macrophages. Luciferase reporter assay was used to confirm the target gene of miR-125a-5p. In mouse experiments, inhibiting miR-125a-5p was utilized to examine its role in macrophage polarization. Furthermore, the underlying mechanism was explored.
Results: In vitro results indicated that CSE treatment led to upregulation of miR-125a-5p in HBE cells, and exosomes contained miR-125a-5p. PKH26-labeled exosomes were internalized by macrophages. Co-culture experiments between bronchial epithelial cells and miR-125a-5p mimic resulted in significant increase in M1 macrophage markers (TNF-α, iNOS-2, IL-1β) and decrease in M2 markers (IL-10 and Arg-1). In COPD mouse models, miR-125a-5p inhibitor reduced levels of TNF-α, IL-1β, and IL-6. Luciferase assays revealed that miR-125a-5p inhibitors enhanced the relative luciferase activity of IL1RN. Mechanistic experiments demonstrated that HBE-derived exosomes transfected with miR-125a-5p mimics promoted upregulation of MyD88, TRAF6, p65, iNOS-2, and downregulation of Arg-1.
Conclusion: This study suggests that exosomal miR-125a-5p may act as a mediator in the cross-talk between airway epithelium and macrophage polarization in COPD. Exosomal miR-125a-5p targeting IL1RN may promote M1 macrophage polarization via the MyD88/NF-κB pathway.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Chronic obstructive pulmonary disease; Epithelium; Exosome; Macrophage polarization; miR-125a-5p
المشرفين على المادة: 0 (Interleukin 1 Receptor Antagonist Protein)
0 (MicroRNAs)
0 (MIRN125 microRNA, human)
0 (Mirn125 microRNA, mouse)
0 (IL1RN protein, human)
0 (Il1rn protein, mouse)
تواريخ الأحداث: Date Created: 20240614 Date Completed: 20240710 Latest Revision: 20240805
رمز التحديث: 20240805
DOI: 10.1016/j.intimp.2024.112466
PMID: 38875998
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-1705
DOI:10.1016/j.intimp.2024.112466