Bone mesenchymal stem cell-derived extracellular vesicles inhibit DAPK1-mediated inflammation by delivering miR-191 to macrophages

• Published in: Biochemical and biophysical research communications 2022-04, Vol.598, p.32-39
• Main Authors: Liu, Hui, Zhang, Luming, Li, Meilian, Zhao, Fengzhi, Lu, Fan, Zhang, Feng, Chen, Sida, Guo, Juntao, Zhang, Rui, Yin, Haiyan
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; Bone mesenchymal stem cell; Culture Media, Conditioned - pharmacology; DAPK1; Death-Associated Protein Kinases - genetics; Extracellular vesicles; Extracellular Vesicles - genetics; Gene Expression Regulation - drug effects; Humans; Inflammation - etiology; Inflammation - genetics; Inflammation factors; Lipopolysaccharides - toxicity; Macrophage Activation - genetics; Macrophage Activation - physiology; Mesenchymal Stem Cells - cytology; MicroRNAs - genetics; MicroRNAs - pharmacology; miR-191; Promoter Regions, Genetic; THP-1 Cells; THP-1 macrophages
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.02.009

Alveolar macrophage activation and apoptosis are vital contributors to sepsis-associated acute lung injury (ALI). However, the mechanisms of alveolar macrophage activation are yet to be clarified. Death-associated protein kinase 1 (DAPK1) is one of the potential candidates that play crucial roles in regulating alveolar macrophage inflammation. Herein, we found that primary human bone mesenchymal stem cell (BMSC)-derived extracellular vesicles (EVs) antagonize LPS-induced inflammation in the THP-1 human macrophage-like cell line. Mechanistically, LPS stimulation elevates the expression of DAPK1 and the inflammation markers in THP-1 cells, while BMSC-derived EVs inhibit the expression of DAPK1 and inflammation through delivering miR-191, which can target the 3′-UTR of the DAPK1 mRNA and therefore suppress its translation. The importance of DAPK1 in the activation of THP-1 is also stressed in this study. Our findings provide evidence that BMSC-derived EVs regulate the alveolar macrophage inflammation and highlight BMSC-derived EVs as a potential vehicle to deliver biomacromolecules to macrophages. -The BMSC-derived EVs inhibit the inflammatory activation of THP-1 cells.-The miR-191 from BMSC-derived EVs inhibits the transcript of DAPK1 in THP-1 cells.-Inactivation of DAPK1 is crucial for inhibiting the activation of THP-1 cells.