Volume 61, Issue 6, Pages 1365-1375 (December 2014) CXCL10 plays a key role as an inflammatory mediator and a non-invasive biomarker of non-alcoholic steatohepatitis  Xiang Zhang, Jiayun Shen, Kwan Man, Eagle S.H. Chu, Tung On Yau, Joanne C.Y. Sung, Minnie Y.Y. Go, Jun Deng, Liwei Lu, Vincent W.S. Wong, Joseph J.Y. Sung, Geoffrey Farrell, Jun Yu  Journal of Hepatology  Volume 61, Issue 6, Pages 1365-1375 (December 2014) DOI: 10.1016/j.jhep.2014.07.006 Copyright © 2014 European Association for the Study of the Liver Terms and Conditions

Fig. 1 Deficiency of CXCL10 attenuates experimental steatohepatitis. (A) Representative H&E staining (arrows, inflammatory cells) and Oil red O staining from 4-week liver sections of Cxcl10−/− and WT mice fed a control or MCD diet. (B) Hepatic CXCL10 mRNA and protein levels in liver tissues of WT mice. (C) Serum ALT, total hepatic lipid peroxide and liver triglyceride content in WT and Cxcl10−/− mice fed control or MCD diet for 4weeks. (D) Collagen deposition by Sirius Red staining and hydroxyproline content of liver sections in mice fed a control or MCD diet for 8weeks. Data are mean±SD, n=5–8/group. ∗p<0.05, ∗∗p<0.001, ∗∗∗p<0.0001 vs. same genotype mice fed control diet. #p<0.01 vs. WT mice fed MCD diet. Journal of Hepatology 2014 61, 1365-1375DOI: (10.1016/j.jhep.2014.07.006) Copyright © 2014 European Association for the Study of the Liver Terms and Conditions

Fig. 2 CXCL10 induces steatohepatitis through hepatic inflammatory molecules, lipogenic factors and oxidative stress. (A) Hepatic TNF-α, IL-1β, and MCP-1 protein levels in mice fed control or MCD diet. (B) NF-κB nuclear binding activity and protein levels of phosphorylated NF-κB subunits p65, p50 and NF-κB suppressor IκBα, (C) protein levels of SREBP-1c, SCD1 and nuclear SREBP-1c DNA binding activity, (D) protein levels of C/EBPβ and nuclear C/EBP DNA binding activity, (E) hepatic CYP2E1 mRNA and protein expression in MCD-fed mice. (F) TUNEL positive cells per 1000 cells and cleaved caspase 3 expression in liver tissues. (G) Schematic diagram for the mechanisms of CXCL10 in the promotion of steatohepatitis. ∗p<0.05, ∗∗p<0.0001 vs. same genotype mice fed control diet. Journal of Hepatology 2014 61, 1365-1375DOI: (10.1016/j.jhep.2014.07.006) Copyright © 2014 European Association for the Study of the Liver Terms and Conditions

Fig. 3 CXCL10 neutralization protects against steatohepatitis in vivo. (A) Representative H&E staining, (B) serum ALT, hepatic triglyceride, lipid hydroperoxide, (C) NF-κB binding activity, phospho NF-κB p65, p50, ICAM-1 levels, (D) CYP2E1 and SREBP-1c expression in mice administrated with anti-CXCL10 or control mAb at 12h before feeding MCD. (E) Liver sections with H&E staining and Oil red O staining, respectively, (F) hepatic triglyceride and lipid peroxidation products (TBARS), (G) TNF-α and ICAM-1 mRNA expression from mice injected with anti-CXCL10 or control mAb at 3weeks after MCD feeding. #p<0.05 vs. mice treated with control mAb. Data are mean±SD, n=5/group. Journal of Hepatology 2014 61, 1365-1375DOI: (10.1016/j.jhep.2014.07.006) Copyright © 2014 European Association for the Study of the Liver Terms and Conditions

Fig. 4 CXCL10 in control and NAFLD patients. (A) Hepatic human CXCL10 mRNA levels; (B) Serum CXCL10 protein levels; (C) Receiver-operating characteristics curves of CXCL10 in diagnosing NAFLD in all subjects, NASH in NAFLD patients and NASH in all subjects. Journal of Hepatology 2014 61, 1365-1375DOI: (10.1016/j.jhep.2014.07.006) Copyright © 2014 European Association for the Study of the Liver Terms and Conditions