title: Hepcidin protects against lipopolysaccharide-induced liver injury in a mouse model of obstructive jaundice.
abstract: Obstructive jaundice (OJ) increases the risk of liver injury and sepsis, leading to increased mortality. Cholestatic liver injury is associated with a downregulation of hepcidin expression levels. In fact, hepcidin has an important antimicrobial effect, especially against Escherichia coli. It is unknown whether supplementing recombinant hepcidin is effective in alleviating cholestasis-induced liver injury and mortality in mice with superimposed sepsis. A mouse model of cholestasis was developed using extrahepatic bile duct ligation for 3 days. In addition, sepsis due to E. coli 0111:B4 lipopolysaccharide (LPS) was induced in the model. The serum levels of total bilirubin, AST, ALT, and LDH and the mRNA levels of IL-1β, TNF-α, and MCP-1 in the liver were significantly higher in the OJ mice receiving LPS than in the sham-operated mice receiving LPS. Compared to the OJ mice receiving LPS, the hepcidin-pretreated OJ mice receiving LPS showed a significant decrease in the above mentioned parameters, as well as a reversal in the downregulation of LC3B-II and upregulation of cleaved caspase-3; this, in turn, led to significantly decreased lethality in 24h. In conclusion, these results indicate that hepcidin pretreatment significantly reduced hepatic proinflammatory cytokine expression and liver injury, leading to reduced early lethality in OJ mice receiving LPS. Enhanced autophagy and reduced apoptosis may account for the protective effects of hepcidin.
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Niao-Sung District, Kaohsiung 833, Taiwan, ROC.
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Huang
authors.forename: Ya-Ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Mao-Meng
authors.initials: MM
authors.lastname: Tiao
authors.forename: Ho-Chang
authors.initials: HC
authors.lastname: Kuo
authors.forename: Li-Tung
authors.initials: LT
authors.lastname: Huang
authors.forename: Jiin-Haur
authors.initials: JH
authors.lastname: Chuang
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects; D001652:Bile Ducts / Q000601:surgery; D018932:Chemokine CCL2 / Q000378:metabolism; D002779:Cholestasis / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D064451:Hepcidins; D053583:Interleukin-1beta / Q000378:metabolism; D041781:Jaundice, Obstructive / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011897:Random Allocation; D011994:Recombinant Proteins / Q000494:pharmacology; D018805:Sepsis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C579599:Hamp protein, mouse; D064451:Hepcidins; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha