Macrosteatosis and necrosis were also often observed in some ethanol-fed mice (Fig. 1D,E). Sirius red and α-SMA staining revealed no obvious liver fibrosis in this model (data not shown). Chronic-binge induced the highest levels of serum ALT and AST compared to 4-week, 10-day ethanol feeding, or single ethanol gavage alone (Fig. 1F). The

detailed comparison of liver injury between chronic-binge and single ethanol gavage alone was further examined (Supporting Information Fig. 2), which clearly showed that chronic-binge induced much higher peak levels of liver injury (ALT and AST) than single ethanol gavage 6 and 9 hours after gavage. Single ethanol gavage alone also elevated hepatic triglyceride levels, which was similar to chronic-binge group (Supporting selleck inhibitor Information Fig. 2B) and consistent with previous reports.26 Fig. 2A shows that chronic-binge but not control group induced liver inflammation as indicated by elevation of inflammatory markers (CCR2 for monocytes; F4/80 for macrophages) and proinflammatory cytokines. Expression of neutrophils marker MPO was undetectable in both groups (data not shown). Serum levels of proinflammatory cytokines were higher in chronic-binge-treated mice than

those with control diet (Fig. 2B). Finally, Fig. 2C shows that compared to the control group, the levels of oxidative stress marker 4-NHE in the liver were elevated whereas hepatic GSH levels were decreased in the chronic-binge group. The expression of hepatic fat metabolism-associated genes was

also examined. As shown in Fig. 3, hepatic expression of several lipogenesis genes selleck chemical (SREBP-1, FAS, LXRα, ACC, and SCD1) was up-regulated whereas fat oxidation gene (PPARα) was decreased in chronic-binge group compared to control groups. To explore the therapeutic potential of IL-22 in treating alcoholic liver disease, pair-fed or chronic-binge-fed mice were treated with IL-22. Liver injury, oxidative stress, and inflammation were then assessed. As illustrated in Fig. 4A,B, treatment with recombinant IL-22 reduced serum ALT and AST as well as liver triglyceride levels but medchemexpress did not affect cholesterol levels. The protective effect of IL-22 on alcoholic fatty liver was further confirmed by liver histology (Fig. 4C). Interestingly, serum levels of triglyceride were elevated after IL-22 treatment whereas cholesterol levels remained unchanged (Fig. 4D). In addition, IL-22 treatment prevented ethanol-mediated induction of 4-NHE and depletion of GSH levels in the liver (Fig. 4E). Finally, IL-22 treatment did not affect the hepatic and serum levels of proinflammatory cytokines from both groups but up-regulated slightly the hepatic expression of F4/80 and CCR2 (Supporting Information Fig. 3). The hepatoprotective effect of IL-22 on alcoholic liver injury was further confirmed by adenovirus IL-22 treatment.