MicroRNA cargo of extracellular vesicles from alcoholexposed monocytes signals naive monocytes to differentiate into M2 macrophages

Banishree Saha, Fatemeh Momen-Heravi, Karen Kodys, G. Szabó

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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 intoM2macrophages as indicated by increased surface expression of CD68 (macrophage marker), M2 markers (CD206 (mannose receptor) and CD163 (scavenger receptor)), secretion of IL-10, and TGFβ 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.Wefound 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, alcoholexposed 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.

Original languageEnglish
Pages (from-to)149-159
Number of pages11
JournalJournal of Biological Chemistry
Volume291
Issue number1
DOIs
Publication statusPublished - Jan 1 2016

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Macrophages
MicroRNAs
Monocytes
Alcohols
Exosomes
Scavenger Receptors
Extracellular Vesicles
Interleukin-10
Biological materials
Coated Vesicles
Alcoholic Hepatitis
Polarization
Membranes
Plasmas
Phagocytosis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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MicroRNA cargo of extracellular vesicles from alcoholexposed monocytes signals naive monocytes to differentiate into M2 macrophages. / Saha, Banishree; Momen-Heravi, Fatemeh; Kodys, Karen; Szabó, G.

In: Journal of Biological Chemistry, Vol. 291, No. 1, 01.01.2016, p. 149-159.

Research output: Contribution to journalArticle

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