title: Neutralization of chemokine CXCL14 (BRAK) expression reduces CCl4 induced liver injury and steatosis in mice.
abstract: Using mouse gene expression microarray analysis, we earlier obtained dynamic profiles of whole genome expression in the CCl(4)-induced liver injury mouse model. CXCL14 expression was increased in the liver injury phase and returned to normal after liver regeneration suggesting its involvement in the liver injury or regeneration regulation. The role of CXCL14 in liver injury was investigated. The dynamic of CXCL14 transcription was analyzed in CCl(4)-induced mouse liver damage by qRT-PCR. Plasmid mediated CXCL14 overexpression and antibody neutralization of endogenous CXCL14 were used to demonstrate its effects and mechanisms on CCl(4)-induced liver injury and acute liver failure. We showed that CXCL14 expression was immediately upregulated post CCl(4) injection with a dose-dependent response. CXCL14 over-expression aggravated CCl(4)-induced liver injuries, evidenced by enhanced acidophilic change and necrosis of hepatocyte, increased fat deposition in hepatocytes (P<0.01), and inhibited hepatocyte proliferation (P<0.01). On the contrary, anti-CXCL14 antibody treatment reduced the severity of CCL4-induced liver injuries Significant reductions in hepatic necrosis area (P<0.05), the liver fat deposition (P<0.01), and the lipid peroxidation measured by serum MDA (P<0.05) were observed. Importantly, the antibody treatment reduced the mouse mortality caused by CCl4-induced liver failure (P<0.05). The data suggest that CXCL14 and its receptor present potential targets for the treatment of liver diseases.
authors: Shanghai Municipality Key Laboratory of Veterinary Medicine and Biotechnology, School of Agriculture and Biology, Shanghai 200240, PR China.
authors: Jingjing
authors: J
authors: Li
authors: Jin
authors: J
authors: Gao
authors: Dejun
authors: D
authors: Yan
authors: Yunsheng
authors: Y
authors: Yuan
authors: Sunita
authors: S
authors: Sah
authors: Uttam
authors: U
authors: Satyal
authors: Man
authors: M
authors: Liu
authors: Wei
authors: W
authors: Han
authors: Yan
authors: Y
authors: Yu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000627:therapeutic use; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D049109:Cell Proliferation; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D007106:Immune Sera / Q000276:immunology; D015227:Lipid Peroxidation / Q000235:genetics / Q000276:immunology; D017093:Liver Failure / Q000139:chemically induced / Q000276:immunology / Q000628:therapy; D008115:Liver Regeneration / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D009336:Necrosis / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D014158:Transcription, Genetic / Q000276:immunology; D014162:Transfection; D015854:Up-Regulation / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; C517518:CXCL14 protein, mouse; D019743:Chemokines, CXC; D005227:Fatty Acids; D007106:Immune Sera; D002251:Carbon Tetrachloride