title: Discrepant roles of CpG ODN on acute alcohol-induced liver injury in mice.
abstract: Increasing evidence suggests that the alcoholic liver injury is associated with activation of Toll-like receptors (TLRs) and the consequent over-production of inflammatory cytokines such as TNF-α. However, few studies have evaluated the effect of CpG ODN, a TLR9 agonist, on alcoholic liver injury. In this study, an animal model of acute alcohol-induced liver injury was established by administering the mice with alcohol at 7 g/kg intragastrically once. Using the model, 2216, an A-type CpG ODN, was found able to dramatically elevate serum ALT levels and aggravate pathological changes of liver in mice. In contrast, 2006, a B-type CpG ODN, caused elevation of serum ALT levels with no visible aggravation of liver pathological changes; YW002, a C-type CpG ODN, caused no elevation of serum ALT levels and seemed able to lessen pathological changes in the liver of the mice. Real-time RT-PCR revealed that 2216 dramatically up-regulated the expression of TLR9 and TNF-α and YW002 was unable to up-regulate expression of TLR9 and TNF-α, instead up-regulate the expression of IFN-α in the livers of the model mice. The data suggest that 2216 could aggravate alcohol-induced liver injury by inducing the up-regulation of hepatic TLR9 and TNF-α and that YW002 could alleviate the pathological changes induced by acute alcohol intake by up-regulating IFN-α, possibly.
authors.affiliation: Department of Molecular Biology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, PR China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Wang
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wu
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Lina
authors.initials: L
authors.lastname: Li
authors.forename: Yongli
authors.initials: Y
authors.lastname: Yu
authors.forename: Liying
authors.initials: L
authors.lastname: Wang
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006519:Hepatitis, Alcoholic / Q000473:pathology*; D016898:Interferon-alpha / Q000096:biosynthesis; D016899:Interferon-beta / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009838:Oligodeoxyribonucleotides / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C408982:CPG-oligonucleotide; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D000469:Alkaline Phosphatase