PMID- 26843922 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160204 LR - 20200930 IS - 2045-3701 (Print) IS - 2045-3701 (Electronic) IS - 2045-3701 (Linking) VI - 6 DP - 2016 TI - The protective or damaging effect of Tumor necrosis factor-alpha in acute liver injury is concentration-dependent. PG - 8 LID - 10.1186/s13578-016-0074-x [doi] LID - 8 AB - BACKGROUND: Inflammatory cytokine is important in modulating injured diseases. Tumor necrosis factor-alpha (TNF-alpha), one of potent inflammatory cytokines, plays a dominant role in host defense reaction. However, the concrete effect of TNF-alpha on acute liver injury is totally unclear. Here we reported the concrete effect and possible mechanisms of TNF-alpha on acute liver injury induced by carbon tetrachloride (CCl4). METHODS: SD male rats were equally divided into nine groups. CCl4 (1 ml/kg) was subcutaneously injected into the rats. Enbrel, a TNF-alpha inhibitor, were intraperitoneally injected at dose of 0, 0.25, 0.5, 1, 2, 4 or 8 mg/kg 15 min before the CCl4 injection. 24 h later, rats were sacrificed. Serum ALT and AST were measured with an autoanalyzer. Serum TNF-alpha were measured by ELISA. HE staining was used to observe the liver tissue morphology. Hepatocellular apoptosis were tested by immunochemistry and Tunnel kit. Inflammatory factors, involve IL-4, IL-6, IL-8, IL-beta and IFN-gamma were detected by RT-PCR. The NF-kappaB signal pathway and anti-apoptotic genes include Bcl-XL, FHC, XIAP and Bcl-2 were measured by western-blotting and RT-PCR. RESULTS: The change of liver function presented an obvious "V" shape in the whole process of persistently increased Enbrel. As Enbrel was increased gradually from 0 to 1 mg/kg, serum TNF-alpha were blocked, ALT and AST were gradually decreased as TNF-alpha as well as the numbers of hepatocellular apoptosis, and were declined to the minimum at 1 mg/kg Enbrel. As Enbrel was increased gradually from 1 to 8 mg/kg, ALT, AST and hepatocellular apoptosis were increased instead, and reached to the maximum at 8 mg/kg Enbrel. HE showed that the seriousness of hepatocellular steatosis was the most at 8 mg/kg Enbrel, and second at 0 mg/kg, the weakest at 1 mg/kg in the acute liver injury. Western-blotting and RT-PCR showed NF-kappaB, p-IkappaBalpha and antiapoptotic genes include Bcl-XL, FHC, XIAP, Bcl-2 were decreased as TNF-alpha was blocked by increased Enbrel. CONCLUSION: Our results suggested that TNF-alpha had a dual role in acute liver injury. It was regulated might via the corporate effect of NF-kappaB signal pawahway and anti-apoptosis. Meanwhile, our findings provide a reference for clinical treatment of acute liver injury. FAU - Dong, Yulong AU - Dong Y AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. FAU - Liu, Yuzhou AU - Liu Y AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. FAU - Kou, Xingrui AU - Kou X AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. FAU - Jing, Yingying AU - Jing Y AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. FAU - Sun, Kai AU - Sun K AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. AD - Central Laboratory of Medical Research, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Sheng, Dandan AU - Sheng D AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. FAU - Yu, Guofeng AU - Yu G AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. FAU - Yu, Dandan AU - Yu D AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. FAU - Zhao, Qiudong AU - Zhao Q AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. FAU - Zhao, Xue AU - Zhao X AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. AD - Central Laboratory of Medical Research, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Li, Rong AU - Li R AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. FAU - Wu, Mengchao AU - Wu M AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. FAU - Wei, Lixin AU - Wei L AD - Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China. LA - eng PT - Journal Article DEP - 20160203 PL - England TA - Cell Biosci JT - Cell & bioscience JID - 101561195 PMC - PMC4739393 OTO - NOTNLM OT - CCl4 OT - Enbrel OT - Liver injury OT - TNF-alpha EDAT- 2016/02/05 06:00 MHDA- 2016/02/05 06:01 PMCR- 2016/02/03 CRDT- 2016/02/05 06:00 PHST- 2015/07/19 00:00 [received] PHST- 2016/01/25 00:00 [accepted] PHST- 2016/02/05 06:00 [entrez] PHST- 2016/02/05 06:00 [pubmed] PHST- 2016/02/05 06:01 [medline] PHST- 2016/02/03 00:00 [pmc-release] AID - 74 [pii] AID - 10.1186/s13578-016-0074-x [doi] PST - epublish SO - Cell Biosci. 2016 Feb 3;6:8. doi: 10.1186/s13578-016-0074-x. eCollection 2016.