Chronic Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis via Immune Disturbances

Abstract Chronic alcohol consumption increases the risk of hepatocellular carcinoma (HCC). However, little is known about the potential immunological mechanisms by which ethanol affects tumor progression. Here, adult male mice were administered multiple doses of diethylnitrosamine (DEN). Four and a...

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Autores principales:	Guoxiu Yan, Xuefu Wang, Cheng Sun, Xiaodong Zheng, Haiming Wei, Zhigang Tian, Rui Sun
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6824d25a08434f0aa403e3b8429d35e3
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spelling	oai:doaj.org-article:6824d25a08434f0aa403e3b8429d35e32021-12-02T15:05:24ZChronic Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis via Immune Disturbances10.1038/s41598-017-02887-72045-2322https://doaj.org/article/6824d25a08434f0aa403e3b8429d35e32017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02887-7https://doaj.org/toc/2045-2322Abstract Chronic alcohol consumption increases the risk of hepatocellular carcinoma (HCC). However, little is known about the potential immunological mechanisms by which ethanol affects tumor progression. Here, adult male mice were administered multiple doses of diethylnitrosamine (DEN). Four and a half months later, the DEN-treated mice were placed on a liquid Lieber-DeCarli control diet or diet containing 5% ethanol for 2.5 months. At the end of the study, liver tissue samples were obtained to analyze pathology, gene expression, and hepatic mononuclear cells (MNCs). Results showed that ethanol feeding exacerbates the progression of hepatic tumors (characterized by the ratio of liver weight to body weight, and the tumor volume and diameter) in DEN-treated mice. Mechanistically, chronic alcohol consumption decreased the number of antitumor CD8+ T cells but increased the number of tumor-associated macrophages (TAMs) in the liver in DEN-initiated tumorigenesis. Besides, TAMs were prone to be M2 phenotype after alcohol consumption. Moreover, chronic alcohol consumption aggravated inflammation, fibrosis, and epithelial-mesenchymal transition (EMT) in the pathological process of HCC. These data demonstrate that chronic alcohol consumption exacerbates DEN-induced hepatocarcinogenesis by enhancing protumor immunity, impairing antitumor immunity and aggravating hepatic pathological injury. Targeting the immune system is a potential therapeutic regimen for alcohol-promoted HCC.Guoxiu YanXuefu WangCheng SunXiaodong ZhengHaiming WeiZhigang TianRui SunNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guoxiu Yan Xuefu Wang Cheng Sun Xiaodong Zheng Haiming Wei Zhigang Tian Rui Sun Chronic Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis via Immune Disturbances
description	Abstract Chronic alcohol consumption increases the risk of hepatocellular carcinoma (HCC). However, little is known about the potential immunological mechanisms by which ethanol affects tumor progression. Here, adult male mice were administered multiple doses of diethylnitrosamine (DEN). Four and a half months later, the DEN-treated mice were placed on a liquid Lieber-DeCarli control diet or diet containing 5% ethanol for 2.5 months. At the end of the study, liver tissue samples were obtained to analyze pathology, gene expression, and hepatic mononuclear cells (MNCs). Results showed that ethanol feeding exacerbates the progression of hepatic tumors (characterized by the ratio of liver weight to body weight, and the tumor volume and diameter) in DEN-treated mice. Mechanistically, chronic alcohol consumption decreased the number of antitumor CD8+ T cells but increased the number of tumor-associated macrophages (TAMs) in the liver in DEN-initiated tumorigenesis. Besides, TAMs were prone to be M2 phenotype after alcohol consumption. Moreover, chronic alcohol consumption aggravated inflammation, fibrosis, and epithelial-mesenchymal transition (EMT) in the pathological process of HCC. These data demonstrate that chronic alcohol consumption exacerbates DEN-induced hepatocarcinogenesis by enhancing protumor immunity, impairing antitumor immunity and aggravating hepatic pathological injury. Targeting the immune system is a potential therapeutic regimen for alcohol-promoted HCC.
format	article
author	Guoxiu Yan Xuefu Wang Cheng Sun Xiaodong Zheng Haiming Wei Zhigang Tian Rui Sun
author_facet	Guoxiu Yan Xuefu Wang Cheng Sun Xiaodong Zheng Haiming Wei Zhigang Tian Rui Sun
author_sort	Guoxiu Yan
title	Chronic Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis via Immune Disturbances
title_short	Chronic Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis via Immune Disturbances
title_full	Chronic Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis via Immune Disturbances
title_fullStr	Chronic Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis via Immune Disturbances
title_full_unstemmed	Chronic Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis via Immune Disturbances
title_sort	chronic alcohol consumption promotes diethylnitrosamine-induced hepatocarcinogenesis via immune disturbances
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6824d25a08434f0aa403e3b8429d35e3
work_keys_str_mv	AT guoxiuyan chronicalcoholconsumptionpromotesdiethylnitrosamineinducedhepatocarcinogenesisviaimmunedisturbances AT xuefuwang chronicalcoholconsumptionpromotesdiethylnitrosamineinducedhepatocarcinogenesisviaimmunedisturbances AT chengsun chronicalcoholconsumptionpromotesdiethylnitrosamineinducedhepatocarcinogenesisviaimmunedisturbances AT xiaodongzheng chronicalcoholconsumptionpromotesdiethylnitrosamineinducedhepatocarcinogenesisviaimmunedisturbances AT haimingwei chronicalcoholconsumptionpromotesdiethylnitrosamineinducedhepatocarcinogenesisviaimmunedisturbances AT zhigangtian chronicalcoholconsumptionpromotesdiethylnitrosamineinducedhepatocarcinogenesisviaimmunedisturbances AT ruisun chronicalcoholconsumptionpromotesdiethylnitrosamineinducedhepatocarcinogenesisviaimmunedisturbances
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Chronic Alcohol Consumption Promotes Diethylnitrosamine-Induced Hepatocarcinogenesis via Immune Disturbances

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