Alcohol-induced miR-27a regulates differentiation and M2 macrophage polarization of normal human monocytes

Banishree Saha, Johanna C. Bruneau, Karen Kodys, G. Szabó

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Alcohol abuse is a leading cause of liver disease characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Immunomodulatory effects of alcohol on monocytes and macrophages contribute to alcoholic liver disease. Alcohol use, an independent risk factor for progression of hepatitis C virus (HCV) infection-mediated liver disease, impairs host defense and alters cytokine production and monocyte/macrophage activation. We hypothesized that alcohol and HCV have synergistic effects on the phenotype and function of monocytes. Our data show that acute alcohol binge drinking in healthy volunteers results in increased frequency of CD16+ and CD68+ and M2-type (CD206+, dendritic cell [DC]-SIGN+-expressing and IL-10-secreting) circulating CD14+ monocytes. Expression of HCV-induced CD68 and M2 markers (CD206 and DC-SIGN) in normal monocytes was further enhanced in the presence of alcohol. The levels of microRNA (miR)-27a was significantly upregulated in monocytes cultured in the presence of alcohol or alcohol and HCV as compared with HCV alone. The functional role of miR-27a in macrophage polarization was demonstrated by transfecting monocytes with an miR-27a inhibitor that resulted in reduced alcohol- and HCV- mediated monocyte activation (CD14 and CD68 expression), polarization (CD206 and DC-SIGN expression), and IL-10 secretion. Over-expression of miR-27a in monocytes enhanced IL-10 secretion via activation of the ERK signaling pathway. We found that miR-27a promoted ERK phosphorylation by downregulating the expression of ERK inhibitor sprouty2 in monocytes. Thus, we identified that sprouty2 is a target of miR-27a in human monocytes. In summary, our study demonstrates the regulatory role of miR-27a in alcohol-induced monocyte activation and polarization.

Original languageEnglish
Pages (from-to)3079-3087
Number of pages9
JournalJournal of Immunology
Volume194
Issue number7
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

MicroRNAs
Monocytes
Macrophages
Alcohols
Hepacivirus
Interleukin-10
Dendritic Cells
Liver Diseases
Alcoholic Hepatitis
Binge Drinking
Alcoholic Liver Cirrhosis
Alcoholic Liver Diseases
Macrophage Activation
MAP Kinase Signaling System
Virus Diseases
Fatty Liver
Alcohol Drinking
Liver Cirrhosis
Alcoholism
Healthy Volunteers

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Alcohol-induced miR-27a regulates differentiation and M2 macrophage polarization of normal human monocytes. / Saha, Banishree; Bruneau, Johanna C.; Kodys, Karen; Szabó, G.

In: Journal of Immunology, Vol. 194, No. 7, 01.04.2015, p. 3079-3087.

Research output: Contribution to journalArticle

Saha, Banishree ; Bruneau, Johanna C. ; Kodys, Karen ; Szabó, G. / Alcohol-induced miR-27a regulates differentiation and M2 macrophage polarization of normal human monocytes. In: Journal of Immunology. 2015 ; Vol. 194, No. 7. pp. 3079-3087.
@article{b0a089f9f2904332846c8056b558f097,
title = "Alcohol-induced miR-27a regulates differentiation and M2 macrophage polarization of normal human monocytes",
abstract = "Alcohol abuse is a leading cause of liver disease characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Immunomodulatory effects of alcohol on monocytes and macrophages contribute to alcoholic liver disease. Alcohol use, an independent risk factor for progression of hepatitis C virus (HCV) infection-mediated liver disease, impairs host defense and alters cytokine production and monocyte/macrophage activation. We hypothesized that alcohol and HCV have synergistic effects on the phenotype and function of monocytes. Our data show that acute alcohol binge drinking in healthy volunteers results in increased frequency of CD16+ and CD68+ and M2-type (CD206+, dendritic cell [DC]-SIGN+-expressing and IL-10-secreting) circulating CD14+ monocytes. Expression of HCV-induced CD68 and M2 markers (CD206 and DC-SIGN) in normal monocytes was further enhanced in the presence of alcohol. The levels of microRNA (miR)-27a was significantly upregulated in monocytes cultured in the presence of alcohol or alcohol and HCV as compared with HCV alone. The functional role of miR-27a in macrophage polarization was demonstrated by transfecting monocytes with an miR-27a inhibitor that resulted in reduced alcohol- and HCV- mediated monocyte activation (CD14 and CD68 expression), polarization (CD206 and DC-SIGN expression), and IL-10 secretion. Over-expression of miR-27a in monocytes enhanced IL-10 secretion via activation of the ERK signaling pathway. We found that miR-27a promoted ERK phosphorylation by downregulating the expression of ERK inhibitor sprouty2 in monocytes. Thus, we identified that sprouty2 is a target of miR-27a in human monocytes. In summary, our study demonstrates the regulatory role of miR-27a in alcohol-induced monocyte activation and polarization.",
author = "Banishree Saha and Bruneau, {Johanna C.} and Karen Kodys and G. Szab{\'o}",
year = "2015",
month = "4",
day = "1",
doi = "10.4049/jimmunol.1402190",
language = "English",
volume = "194",
pages = "3079--3087",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Alcohol-induced miR-27a regulates differentiation and M2 macrophage polarization of normal human monocytes

AU - Saha, Banishree

AU - Bruneau, Johanna C.

AU - Kodys, Karen

AU - Szabó, G.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Alcohol abuse is a leading cause of liver disease characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Immunomodulatory effects of alcohol on monocytes and macrophages contribute to alcoholic liver disease. Alcohol use, an independent risk factor for progression of hepatitis C virus (HCV) infection-mediated liver disease, impairs host defense and alters cytokine production and monocyte/macrophage activation. We hypothesized that alcohol and HCV have synergistic effects on the phenotype and function of monocytes. Our data show that acute alcohol binge drinking in healthy volunteers results in increased frequency of CD16+ and CD68+ and M2-type (CD206+, dendritic cell [DC]-SIGN+-expressing and IL-10-secreting) circulating CD14+ monocytes. Expression of HCV-induced CD68 and M2 markers (CD206 and DC-SIGN) in normal monocytes was further enhanced in the presence of alcohol. The levels of microRNA (miR)-27a was significantly upregulated in monocytes cultured in the presence of alcohol or alcohol and HCV as compared with HCV alone. The functional role of miR-27a in macrophage polarization was demonstrated by transfecting monocytes with an miR-27a inhibitor that resulted in reduced alcohol- and HCV- mediated monocyte activation (CD14 and CD68 expression), polarization (CD206 and DC-SIGN expression), and IL-10 secretion. Over-expression of miR-27a in monocytes enhanced IL-10 secretion via activation of the ERK signaling pathway. We found that miR-27a promoted ERK phosphorylation by downregulating the expression of ERK inhibitor sprouty2 in monocytes. Thus, we identified that sprouty2 is a target of miR-27a in human monocytes. In summary, our study demonstrates the regulatory role of miR-27a in alcohol-induced monocyte activation and polarization.

AB - Alcohol abuse is a leading cause of liver disease characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Immunomodulatory effects of alcohol on monocytes and macrophages contribute to alcoholic liver disease. Alcohol use, an independent risk factor for progression of hepatitis C virus (HCV) infection-mediated liver disease, impairs host defense and alters cytokine production and monocyte/macrophage activation. We hypothesized that alcohol and HCV have synergistic effects on the phenotype and function of monocytes. Our data show that acute alcohol binge drinking in healthy volunteers results in increased frequency of CD16+ and CD68+ and M2-type (CD206+, dendritic cell [DC]-SIGN+-expressing and IL-10-secreting) circulating CD14+ monocytes. Expression of HCV-induced CD68 and M2 markers (CD206 and DC-SIGN) in normal monocytes was further enhanced in the presence of alcohol. The levels of microRNA (miR)-27a was significantly upregulated in monocytes cultured in the presence of alcohol or alcohol and HCV as compared with HCV alone. The functional role of miR-27a in macrophage polarization was demonstrated by transfecting monocytes with an miR-27a inhibitor that resulted in reduced alcohol- and HCV- mediated monocyte activation (CD14 and CD68 expression), polarization (CD206 and DC-SIGN expression), and IL-10 secretion. Over-expression of miR-27a in monocytes enhanced IL-10 secretion via activation of the ERK signaling pathway. We found that miR-27a promoted ERK phosphorylation by downregulating the expression of ERK inhibitor sprouty2 in monocytes. Thus, we identified that sprouty2 is a target of miR-27a in human monocytes. In summary, our study demonstrates the regulatory role of miR-27a in alcohol-induced monocyte activation and polarization.

UR - http://www.scopus.com/inward/record.url?scp=84925858227&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925858227&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1402190

DO - 10.4049/jimmunol.1402190

M3 - Article

C2 - 25716995

AN - SCOPUS:84925858227

VL - 194

SP - 3079

EP - 3087

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -