| Literature DB >> 32051339 |
Jun Xu1,2, Hsiao-Yen Ma1, Xiao Liu1,2, Sara Rosenthal1, Jacopo Baglieri1,2, Ryan McCubbin1, Mengxi Sun1, Yukinori Koyama1,2, Cedric G Geoffroy3,4, Kaoru Saijo5, Linshan Shang2, Takahiro Nishio2, Igor Maricic1, Max Kreifeldt6, Praveen Kusumanchi7,8, Amanda Roberts6, Binhai Zheng3, Vipin Kumar1, Karsten Zengler9, Donald P Pizzo10, Mojgan Hosseini10, Candice Contet6, Christopher K Glass11, Suthat Liangpunsakul7,8,12, Hidekazu Tsukamoto13,14, Bin Gao15, Michael Karin16, David A Brenner1, George F Koob17, Tatiana Kisseleva2.
Abstract
Chronic alcohol abuse has a detrimental effect on the brain and liver. There is no effective treatment for these patients, and the mechanism underlying alcohol addiction and consequent alcohol-induced damage of the liver/brain axis remains unresolved. We compared experimental models of alcoholic liver disease (ALD) and alcohol dependence in mice and demonstrated that genetic ablation of IL-17 receptor A (IL-17ra-/-) or pharmacological blockade of IL-17 signaling effectively suppressed the increased voluntary alcohol drinking in alcohol-dependent mice and blocked alcohol-induced hepatocellular and neurological damage. The level of circulating IL-17A positively correlated with the alcohol use in excessive drinkers and was further increased in patients with ALD as compared with healthy individuals. Our data suggest that IL-17A is a common mediator of excessive alcohol consumption and alcohol-induced liver/brain injury, and targeting IL-17A may provide a novel strategy for treatment of alcohol-induced pathology.Entities:
Keywords: Addiction; Fibrosis; Gastroenterology; Mouse models
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Year: 2020 PMID： 32051339 PMCID： PMC7098802 DOI： 10.1172/jci.insight.131277
Source DB: PubMed Journal: JCI Insight ISSN： 2379-3708