title: C-C chemokine receptor type 5 deficiency exacerbates alcoholic fatty liver disease through pro-inflammatory cytokines and chemokines-induced hepatic inflammation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Deficiency of CCR5 exacerbates alcoholic fatty liver disease by hepatic inflammation induced by pro-inflammatory cytokines and chemokines and oxidative stress.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea.
authors.forename: Ju Ho
authors.initials: JH
authors.lastname: Park
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea.
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Raw Material Synthetic Factory, Dongkook Pharmaceutical company, Jincheon-gun, Korea.
authors.forename: Mork Soon
authors.initials: MS
authors.lastname: Park
authors.affiliation: College of Pharmacy, Pusan National University, Busan, Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Jung
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D018450:Disease Progression; D005235:Fatty Liver, Alcoholic / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D019713:Receptors, CCR5 / Q000172:deficiency*
chemical_list: C584933:CCR5 protein, human; D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D019713:Receptors, CCR5
keywords: CCR5; cytokine; hepatic inflammation; lipid accumulation