UMMS Affiliation

Department of Medicine, Division of Gastroenterology

Date

5-14-2015

Document Type

Article

Subjects

Alcoholism; Animals; *Binge Drinking; Cell Communication; Cell Line; Ethanol; Exosomes; Female; Hepatocytes; Humans; Inflammation; Lipopolysaccharides; Liver; Macrophages; Male; Mice; Mice, Inbred C57BL; MicroRNAs; RNA Interference; RNA, Small Interfering

Disciplines

Cell Biology | Cellular and Molecular Physiology | Gastroenterology

Abstract

Hepatocyte damage and inflammation in monocytes/macrophages are central to the pathogenesis of alcoholic hepatitis (AH). MicroRNAs (miRNAs) regulate all of these processes. MiRNA-122 is abundantly expressed in hepatocytes while monocytes/macrophages have low levels. The role of exosomes in AH and possible cross talk between hepatocyte-derived exosomes and immune cells is not explored yet. Here, we show that the number of exosomes significantly increases in the sera of healthy individuals after alcohol binge drinking and in mice after binge or chronic alcohol consumption. Exosomes isolated from sera after alcohol consumption or from in vitro ethanol-treated hepatocytes contained miRNA-122. Exosomes derived from ethanol-treated Huh7.5 cells were taken up by the recipients THP1 monocytes and horizontally transferred a mature form of liver-specific miRNA-122. In vivo, liver mononuclear cells and Kupffer cells from alcohol-fed mice had increased miRNA-122 levels. In monocytes, miRNA-122 transferred via exosomes inhibited the HO-1 pathway and sensitized to LPS stimulation and increased levels of pro-inflammatory cytokines. Finally, inflammatory effects of exosomes from ethanol-treated hepatocytes were prevented by using RNA interference via exosome-mediated delivery of a miRNA-122 inhibitor. These results demonstrate that first, exosomes mediate communication between hepatocytes and monocytes/macrophages and second, hepatocyte-derived miRNA-122 can reprogram monocytes inducing sensitization to LPS.

Rights and Permissions

Citation: Sci Rep. 2015 May 14;5:9991. doi: 10.1038/srep09991. Link to article on publisher's site

DOI of Published Version

10.1038/srep09991

Comments

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Related Resources

Link to Article in PubMed

Keywords

Inflammatory diseases, miRNAs

Journal Title

Scientific reports

PubMed ID

25973575

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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