title: The protective or damaging effect of Tumor necrosis factor-α in acute liver injury is concentration-dependent.
abstract: BACKGROUND
  Inflammatory cytokine is important in modulating injured diseases. Tumor necrosis factor-α (TNF-α), one of potent inflammatory cytokines, plays a dominant role in host defense reaction. However, the concrete effect of TNF-α on acute liver injury is totally unclear. Here we reported the concrete effect and possible mechanisms of TNF-α 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-α 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-α 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-β and IFN-γ were detected by RT-PCR. The NF-κB 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-α were blocked, ALT and AST were gradually decreased as TNF-α 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-κB, p-IκBα and antiapoptotic genes include Bcl-XL, FHC, XIAP, Bcl-2 were decreased as TNF-α was blocked by increased Enbrel.
  
  
  CONCLUSIONS
  Our results suggested that TNF-α had a dual role in acute liver injury. It was regulated might via the corporate effect of NF-κB signal pawahway and anti-apoptosis. Meanwhile, our findings provide a reference for clinical treatment of acute liver injury.
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Yulong
authors: Y
authors: Dong
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Yuzhou
authors: Y
authors: Liu
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Xingrui
authors: X
authors: Kou
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Yingying
authors: Y
authors: Jing
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.|Central Laboratory of Medical Research, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Kai
authors: K
authors: Sun
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Dandan
authors: D
authors: Sheng
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Guofeng
authors: G
authors: Yu
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Dandan
authors: D
authors: Yu
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Qiudong
authors: Q
authors: Zhao
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.|Central Laboratory of Medical Research, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Xue
authors: X
authors: Zhao
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Rong
authors: R
authors: Li
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Mengchao
authors: M
authors: Wu
authors: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
authors: Lixin
authors: L
authors: Wei
keywords: CCl4; Enbrel; Liver injury; TNF-α