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dc.contributor.authorSaha, Banishree
dc.contributor.authorMomen-Heravi, Fatemeh
dc.contributor.authorKodys, Karen
dc.contributor.authorSzabo, Gyongyi
dc.date2022-08-11T08:08:33.000
dc.date.accessioned2022-08-23T15:59:08Z
dc.date.available2022-08-23T15:59:08Z
dc.date.issued2016-01-01
dc.date.submitted2016-02-24
dc.identifier.citationJ Biol Chem. 2016 Jan 1;291(1):149-59. doi: 10.1074/jbc.M115.694133. Epub 2015 Nov 2. <a href="http://dx.doi.org/10.1074/jbc.M115.694133">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Linking)
dc.identifier.doi10.1074/jbc.M115.694133
dc.identifier.pmid26527689
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30594
dc.description.abstractMembrane-coated extracellular vesicles (EVs) released by cells can serve as vehicles for delivery of biological materials and signals. Recently, we demonstrated that alcohol-treated hepatocytes cross-talk with immune cells via exosomes containing microRNA (miRNAs). Here, we hypothesized that alcohol-exposed monocytes can communicate with naive monocytes via EVs. We observed increased numbers of EVs, mostly exosomes, secreted by primary human monocytes and THP-1 monocytic cells in the presence of alcohol in a concentration- and time-dependent manner. EVs derived from alcohol-treated monocytes stimulated naive monocytes to polarize into M2 macrophages as indicated by increased surface expression of CD68 (macrophage marker), M2 markers (CD206 (mannose receptor) and CD163 (scavenger receptor)), secretion of IL-10, and TGFbeta and increased phagocytic activity. miRNA profiling of the EVs derived from alcohol-treated THP-1 monocytes revealed high expression of the M2-polarizing miRNA, miR-27a. Treatment of naive monocytes with control EVs overexpressing miR-27a reproduced the effect of EVs from alcohol-treated monocytes on naive monocytes and induced M2 polarization, suggesting that the effect of alcohol EVs was mediated by miR-27a. We found that miR-27a modulated the process of phagocytosis by targeting CD206 expression on monocytes. Importantly, analysis of circulating EVs from plasma of alcoholic hepatitis patients revealed increased numbers of EVs that contained high levels of miR-27a as compared with healthy controls. Our results demonstrate the following: first, alcohol increases EV production in monocytes; second, alcohol-exposed monocytes communicate with naive monocytes via EVs; and third, miR-27a cargo in monocyte-derived EVs can program naive monocytes to polarize into M2 macrophages.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26527689&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1074/jbc.M115.694133
dc.subjectalcoholic hepatitis
dc.subjectcell signaling
dc.subjectexosome (vesicle)
dc.subjectextracellular vesicles
dc.subjectliver injury
dc.subjectphagocytosis
dc.subjectBiochemistry
dc.subjectCellular and Molecular Physiology
dc.subjectDigestive System Diseases
dc.subjectGastroenterology
dc.titleMicroRNA Cargo of Extracellular Vesicles from Alcohol-exposed Monocytes Signals Naive Monocytes to Differentiate into M2 Macrophages
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume291
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/873
dc.identifier.contextkey8205600
html.description.abstract<p>Membrane-coated extracellular vesicles (EVs) released by cells can serve as vehicles for delivery of biological materials and signals. Recently, we demonstrated that alcohol-treated hepatocytes cross-talk with immune cells via exosomes containing microRNA (miRNAs). Here, we hypothesized that alcohol-exposed monocytes can communicate with naive monocytes via EVs. We observed increased numbers of EVs, mostly exosomes, secreted by primary human monocytes and THP-1 monocytic cells in the presence of alcohol in a concentration- and time-dependent manner. EVs derived from alcohol-treated monocytes stimulated naive monocytes to polarize into M2 macrophages as indicated by increased surface expression of CD68 (macrophage marker), M2 markers (CD206 (mannose receptor) and CD163 (scavenger receptor)), secretion of IL-10, and TGFbeta and increased phagocytic activity. miRNA profiling of the EVs derived from alcohol-treated THP-1 monocytes revealed high expression of the M2-polarizing miRNA, miR-27a. Treatment of naive monocytes with control EVs overexpressing miR-27a reproduced the effect of EVs from alcohol-treated monocytes on naive monocytes and induced M2 polarization, suggesting that the effect of alcohol EVs was mediated by miR-27a. We found that miR-27a modulated the process of phagocytosis by targeting CD206 expression on monocytes. Importantly, analysis of circulating EVs from plasma of alcoholic hepatitis patients revealed increased numbers of EVs that contained high levels of miR-27a as compared with healthy controls. Our results demonstrate the following: first, alcohol increases EV production in monocytes; second, alcohol-exposed monocytes communicate with naive monocytes via EVs; and third, miR-27a cargo in monocyte-derived EVs can program naive monocytes to polarize into M2 macrophages.</p>
dc.identifier.submissionpathfaculty_pubs/873
dc.contributor.departmentUMass Metabolic Network
dc.contributor.departmentDepartment of Medicine, Division of Gastroenterology
dc.source.pages149-59


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