Discrepant roles of CpG ODN on acute alcohol-induced liver injury in mice

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-alpha. 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-alpha and YW002 was unable to up-regulate expression of TLR9 and TNF-alpha, instead up-regulate the expression of IFN-alpha 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-alpha and that YW002 could alleviate the pathological changes induced by acute alcohol intake by up-regulating IFN-alpha, possibly. (C) 2012 Elsevier B.V. All rights reserved.