Blockade of IL-17 signaling reverses alcohol-induced liver injury and excessive alcohol drinking in mice
Jun Xu,Hsiao-Yen Ma,Xiao Liu,Sara Brin Rosenthal,Jacopo Baglieri,Ryan McCubbin,Mengxi Sun,Yukinori Koyama,Cédric G. Geoffroy,Cédric G. Geoffroy,Kaoru Saijo,Linshan Shang,Takahiro Nishio,Igor Maricic,Max Kreifeldt,Praveen Kusumanchi,Praveen Kusumanchi,Amanda J. Roberts,Binhai Zheng,Vipin Kumar,Karsten Zengler,Donald P. Pizzo,Mojgan Hosseini,Candice Contet,Christopher K. Glass,Suthat Liangpunsakul,Suthat Liangpunsakul,Hidekazu Tsukamoto,Bin Gao,Michael Karin,David A. Brenner,George F. Koob,Tatiana Kisseleva +32 more
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TLDR
It is suggested 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.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.read more
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Immunopathobiology and therapeutic targets related to cytokines in liver diseases
Yong He,Seonghwan Hwang,Yeni Ait Ahmed,Yeni Ait Ahmed,Dechun Feng,Na Li,Marcelle de Carvalho Ribeiro,Fouad Lafdil,Tatiana Kisseleva,Gyongyi Szabo,Bin Gao +10 more
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