University of Massachusetts Medical School Faculty Publications

Title

MicroRNA Cargo of Extracellular Vesicles from Alcohol-exposed Monocytes Signals Naive Monocytes to Differentiate into M2 Macrophages

UMMS Affiliation

Department of Medicine, Division of Gastroenterology; UMass Metabolic Network

Publication Date

1-1-2016

Document Type

Article

Disciplines

Biochemistry | Cellular and Molecular Physiology | Digestive System Diseases | Gastroenterology

Abstract

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.

Keywords

alcoholic hepatitis, cell signaling, exosome (vesicle), extracellular vesicles, liver injury, phagocytosis

Rights and Permissions

Citation: J Biol Chem. 2016 Jan 1;291(1):149-59. doi: 10.1074/jbc.M115.694133. Epub 2015 Nov 2. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

The Journal of biological chemistry

PubMed ID

26527689