Alcohol consumption is a major etiology of chronic liver disease worldwide. The morphological spectrum of human alcoholic liver disease includes fatty liver, alcoholic hepatitis, and cirrhosis. In rodents, intragastric infusion of ethanol for 4-5 weeks leads to steatosis, inflammation, and to a less extent fibrosis in the liver, whereas feeding Lieber-DeCarli liquid diet containing ethanol does not cause significant liver injury except steatosis. In humans, interestingly, only a small percentage of heavy drinkers (10-15%) developed alcoholic liver injury, strongly suggesting that alcohol is a cofactor for developing chronic liver disease. Accumulating evidence suggests that many genetic and acquired factors are implicated in the susceptibility of the individual to alcohol-induced liver injury. It has been well documented that alcohol consumption accelerates the development and progression of liver disease induced by hepatitis virus infection. Our lab is to study how chronic ethanol consumption potentiates liver injury induced by other toxins or viruses and to study the molecular mechanisms underlying alcohol-induced liver injury. We have demonstrated that IL-6 plays an important role in protecting against liver injury in several murine models of alcoholic liver injury, nonalcoholic fatty liver disease, fatty liver transplantation, and T cell hepatitis. Our findings also showed that treatment with IL-6 ameliorates fatty liver disease in alcohol-fed mice, high-fatdiet fed mice, and genetically modified ob/ob mice. It is believed that the action of IL-6 is mediated via activation of signal transducer and activator of transcription 3 (STAT3). Currently, we are exploring the molecular mechanisms underlying the protective effect of IL-6 in fatty liver disease by using liver specific and macrophage/neutrophil-specific STAT3 knock out mice.? ? In addition, we are also collaborating with Dr. George Kunos and Dr. Pal Pacher from NIAAA to investigate the role of canabinoid in alcoholic liver disease, and with Dr. Jake Liang from NIDDK to study the interaction of alcohol and hepatitis viral proteins in liver injury.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Intramural Research (Z01)
Project #
1Z01AA000369-06
Application #
7591944
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2007
Total Cost
$600,071
Indirect Cost
Name
National Institute on Alcohol Abuse and Alcoholism
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Oh, Yumin; Park, Ogyi; Swierczewska, Magdalena et al. (2016) Systemic PEGylated TRAIL treatment ameliorates liver cirrhosis in rats by eliminating activated hepatic stellate cells. Hepatology 64:209-23
Park, Ogyi; Jeong, Won-Il; Wang, Lei et al. (2009) Diverse roles of invariant natural killer T cells in liver injury and fibrosis induced by carbon tetrachloride. Hepatology 49:1683-94
Jeong, Won-Il; Gao, Bin (2008) Innate immunity and alcoholic liver fibrosis. J Gastroenterol Hepatol 23 Suppl 1:S112-8
Oh, Yeo Kyoung; Lee, Hyun Jung; Jeong, Mi-Hee et al. (2008) Role of activating transcription factor 3 on TAp73 stability and apoptosis in paclitaxel-treated cervical cancer cells. Mol Cancer Res 6:1232-49
Kunos, George; Gao, Bin (2008) Endocannabinoids, CB1 receptors, and liver disease: hitting more than one bird with the same stone. Gastroenterology 134:622-5
Batkai, Sandor; Osei-Hyiaman, Douglas; Pan, Hao et al. (2007) Cannabinoid-2 receptor mediates protection against hepatic ischemia/reperfusion injury. FASEB J 21:1788-800
Moh, Akira; Iwamoto, Yoshiki; Chai, Gui-Xuan et al. (2007) Role of STAT3 in liver regeneration: survival, DNA synthesis, inflammatory reaction and liver mass recovery. Lab Invest 87:1018-28
Horiguchi, Norio; Ishac, Edward J N; Gao, Bin (2007) Liver regeneration is suppressed in alcoholic cirrhosis: correlation with decreased STAT3 activation. Alcohol 41:271-80
Cui, Yongzhi; Hosui, Atsushi; Sun, Rui et al. (2007) Loss of signal transducer and activator of transcription 5 leads to hepatosteatosis and impaired liver regeneration. Hepatology 46:504-13
Donohue Jr, Terrence M; Cederbaum, Arthur I; French, Samuel W et al. (2007) Role of the proteasome in ethanol-induced liver pathology. Alcohol Clin Exp Res 31:1446-59

Showing the most recent 10 out of 20 publications