Interleukin-6 Is an Important Mediator for Mitochondrial DNA Repair After Alcoholic Liver Injury in Mice

Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hepatology (Impact Factor: 11.06). 12/2010; 52(6):2137-47. DOI: 10.1002/hep.23909
Source: PubMed


We investigated the hypothesis that a prominent effect of chronic ethanol consumption is mitochondrial DNA (mtDNA) injury and compared this injury in IL-6 knockout (KO) and wild-type (WT) mice. Ethanol feeding for 4 weeks resulted in steatosis and oxidative mtDNA damage (8-OHdG) in both IL-6KO and WT mice. However, the WT mice were able to repair the injury by increased production of mtDNA repair enzymes (OGG-1, Neil 1) and check point (p21, p53) proteins and avoid the mtDNA mutations. By contrast the IL-6 KO mice were unable to repair mtDNA resulting in deletions and diminished transcription of the mtDNA encoded protein cytochrome c oxidase subunit-I (COI). The mitochondrial injury was reflected by decreased membrane potential, reduced levels of ATP, and apoptosis-inducing factor (AIF)-induced apoptosis. Conclusion: IL-6 plays a critical role in allowing the liver to recover from significant mtDNA oxidation caused by alcohol. The data suggests that IL-6 activates mtDNA repair enzymes and induces cell cycle arrest allowing time for mtDNA repair.

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Available from: Masayuki Hisada, Feb 03, 2015
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