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Text
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URL Address
<a href="http://doi.org/10.1136/gutjnl-2016-311861" target="_blank" rel="noreferrer noopener">http://doi.org/10.1136/gutjnl-2016-311861</a>
Pages
705–715
Issue
4
Volume
66
Dublin Core
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Title
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MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the
Publisher
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Gut
Date
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2017
2017-04
Subject
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*CYTOKINES; *ETHANOL; *FATTY LIVER; *INFLAMMATION; *LEUKOCYTES; Adult; Alanine Transaminase/blood; Alcoholic/genetics/*metabolism/pathology; Alcoholism/*blood/complications; Animals; Aspartate Aminotransferases/blood; Bilirubin/blood; Binge Drinking/*blood/complications; Case-Control Studies; Central Nervous System Depressants/administration & dosage; Down-Regulation; Ethanol/administration & dosage; Female; Humans; Inbred C57BL; Interleukin-6/genetics/metabolism; Liver Diseases; Male; Mice; MicroRNAs/*blood/*genetics; Middle Aged; NADPH Oxidases/genetics/metabolism; Neutrophils/*metabolism; Reactive Oxygen Species/metabolism; Up-Regulation; Young Adult
Creator
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Li Man; He Yong; Zhou Zhou; Ramirez Teresa; Gao Yueqiu; Gao Yanhang; Ross Ruth A; Cao Haixia; Cai Yan; Xu Ming-Jiang; Feng Dechun; Zhang Ping; Liangpunsakul Suthat; Gao Bin
Description
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OBJECTIVES: Chronic-plus-binge ethanol feeding activates neutrophils and exacerbates liver injury in mice. This study investigates how recent excessive drinking affects peripheral neutrophils and liver injury in alcoholics, and how miR-223, one of the most abundant microRNAs (miRNAs) in neutrophils, modulates neutrophil function and liver injury in ethanol-fed mice. DESIGNS: Three hundred alcoholics with (n=140) or without (n=160) recent excessive drinking and 45 healthy controls were enrolled. Mice were fed an ethanol diet for 10 days followed by a single binge of ethanol. RESULTS: Compared with healthy controls or alcoholics without recent drinking, alcoholics with recent excessive drinking had higher levels of circulating neutrophils, which correlated with serum levels of alanine transaminase (ALT) and aspartate transaminase (AST). miRNA array analysis revealed that alcoholics had elevated serum miR-223 levels compared with healthy controls. In chronic-plus-binge ethanol feeding mouse model, the levels of miR-223 were increased in both serum and neutrophils. Genetic deletion of the miR-223 gene exacerbated ethanol-induced hepatic injury, neutrophil infiltration, reactive oxygen species (ROS) and upregulated hepatic expression of interleukin (IL)-6 and phagocytic oxidase (phox) p47(phox). Mechanistic studies revealed that miR-223 directly inhibited IL-6 expression and subsequently inhibited p47(phox) expression in neutrophils. Deletion of the p47(phox) gene ameliorated ethanol-induced liver injury and ROS production by neutrophils. Finally, miR-223 expression was downregulated, while IL-6 and p47(phox) expression were upregulated in peripheral blood neutrophils from alcoholics compared with healthy controls. CONCLUSIONS: miR-223 is an important regulator to block neutrophil infiltration in alcoholic liver disease and could be a novel therapeutic target for the treatment of this malady.
Identifier
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<a href="http://doi.org/10.1136/gutjnl-2016-311861" target="_blank" rel="noreferrer noopener">10.1136/gutjnl-2016-311861</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*CYTOKINES
*ETHANOL
*FATTY LIVER
*Inflammation
*LEUKOCYTES
2017
Adult
Alanine Transaminase/blood
Alcoholic/genetics/*metabolism/pathology
Alcoholism/*blood/complications
Animals
Aspartate Aminotransferases/blood
Bilirubin/blood
Binge Drinking/*blood/complications
Cai Yan
Cao Haixia
Case-Control Studies
Central Nervous System Depressants/administration & dosage
Department of Integrative Medical Sciences
Department of Pharmaceutical Sciences
Down-Regulation
Ethanol/administration & dosage
Female
Feng Dechun
Gao Bin
Gao Yanhang
Gao Yueqiu
Gut
He Yong
Humans
Inbred C57BL
Interleukin-6/genetics/metabolism
Li Man
Liangpunsakul Suthat
Liver Diseases
Male
Mice
MicroRNAs/*blood/*genetics
Middle Aged
NADPH Oxidases/genetics/metabolism
NEOMED College of Medicine
NEOMED College of Pharmacy
Neutrophils/*metabolism
Ramirez Teresa
Reactive Oxygen Species/metabolism
Ross Ruth A
Up-Regulation
Xu Ming-Jiang
Young Adult
Zhang Ping
Zhou Zhou