C‐C chemokine receptor type 5 deficiency exacerbates alcoholic fatty liver disease through pro‐inflammatory cytokines and chemokines‐induced hepatic inflammation

• Published in: Journal of gastroenterology and hepatology Vol. 32; no. 6; pp. 1258 - 1264
• Main Authors: Park, Ju Ho, Lee, Dong Hun, Park, Mork Soon, Jung, Young Suk, Hong, Jin Tae
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.06.2017
• Subjects: Alanine; Alanine transaminase; Animals; Aspartate aminotransferase; CCL3 protein; CCL4 protein; CCR5; CCR5 protein; Chemokine receptors; Chemokines; Chemokines - metabolism; cytokine; Cytokines; Cytokines - metabolism; Dextrin; Disease Progression; Ethanol; Fatty liver; Fatty Liver, Alcoholic - etiology; Fatty Liver, Alcoholic - metabolism; hepatic inflammation; Hepatitis; Humans; Inflammation; Inflammation Mediators - metabolism; Interleukin 6; lipid accumulation; Lipid Metabolism; Lipids; Liver - metabolism; Liver diseases; Male; Maltose; Mice, Knockout; Monocyte chemoattractant protein 1; Oxidative Stress; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptors, CCR5 - deficiency; Rodents; Serum levels; Tumor necrosis factor; cytokine; hepatic inflammation; CCR5; lipid accumulation
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/jgh.13657

Background and Aim Chemokines and chemokine receptors implicated with alcoholic liver disease. Studies have shown that inflammation and oxidative stress induce fat molecules aggregation in liver. We evaluated the relationship between alcoholic fatty liver disease and C‐C chemokine receptor 5 (CCR5) and impact of inflammation and oxidative stress in fat molecule deposition. Methods Lieber–DeCarli diet containing ethanol or isocaloric control diets were fed to wild‐type and CCR5 knockout mice for 10 days and gavaged with a single dose of ethanol or isocaloric maltose dextrin at 11th day. Cytokine, chemokine, and reactive oxygen species levels were measured in liver tissues to study the role of CCR5 in alcoholic fatty liver disease. Results C‐C chemokine receptor type 5 knockout mice exacerbated ethanol‐induced liver injury. Serum levels of aspartate aminotransferase and alanine aminotransferase were higher in CCR5 knockout mice than wild‐type mice, and CCR5 knockout mice showed more severe lipid accumulation in liver tissue than wild‐type mice after ethanol feeding. Increased expressions of pro‐inflammatory cytokines TNF‐α and IL‐6 and chemokines CCL2, CCL3, CCL4, and CCL5 result in exacerbation of hepatitis in CCR5 knockout mice after ethanol feeding. Oxidative stress induced by reactive oxygen species was more severe in CCR5 knockout mice, and increasing level of fatty acid import and decreasing level of lipid degradation resulted in lipid accumulation in ethanol‐fed CCR5 knockout mice. Conclusion Deficiency of CCR5 exacerbates alcoholic fatty liver disease by hepatic inflammation induced by pro‐inflammatory cytokines and chemokines and oxidative stress.