title: The enhanced expression of death receptor 5 (DR5) mediated by HBV X protein through NF-kappaB pathway is associated with cell apoptosis induced by (TNF-α related apoptosis inducing ligand) TRAIL in hepatoma cells.
abstract: BACKGROUND
  HBV X protein (HBX) is associated with cell apoptosis mediated by TNF-α related apoptosis inducing ligand (TRAIL), while the role of HBX on the expressions of TRAIL receptors death receptor 4 (DR4) and DR5 are unclear. In this study, we detected the cell apoptosis induced by TRAIL as well as gene and protein expressions of DR4 and DR5 in Huh-7 cells steadily transfected with HBX (Huh-7-HBX cells). In addition, we investigated the activation of different pathways associated with the expressions of TRAIL receptors in Huh-7-HBX cells.
  
  
  METHODS
  The apoptosis of Huh-7-HBX cells induced by TRAIL was evaluated by flow cytometry analysis. The levels of DR4 and DR5 expression in cells were determined by real-time PCR and western blotting analysis. The activities of JNK pathway and NF-kappaB (NF-κB) pathway were demonstrated by western blotting assay.
  
  
  RESULTS
  Compared to control cells, the percentage of cell apoptosis was increased in Huh-7-HBX cells. The increased expressions of DR4 and DR5 on gene and protein levels were observed in Huh-7-HBX cells. Further researches suggested that activation of JNK pathway was increased but not involved in the expression of TRAIL receptors in HBX positive cells. The activation of NF-κB pathway increased and was responsible for DR5 expression and cell apoptosis in HBX positive cells.
  
  
  CONCLUSIONS
  These results demonstrate that increased apoptosis induced by TRAIL is associated with increased expression of DR5 that mediated by HBX through NF-κB pathway. This finding provides a critical insight into the mechanism of hepatocyte apoptosis mediated by HBX in HBV infection.
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. kong.fanyun@163.com.
authors.forename: Fanyun
authors.initials: F
authors.lastname: Kong
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. youhongjuan_00@163.com.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: You
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. hdzhaojinjin@163.com.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. liuwen0727@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. hlin0123@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. luowy06@163.com.
authors.forename: Wenya
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. m13775989787@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. tangrexian-t@163.com.
authors.forename: Renxian
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. zky02@163.com.
authors.forename: Kuiyang
authors.initials: K
authors.lastname: Zheng
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002460:Cell Line; D005434:Flow Cytometry; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000502:physiology / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D016328:NF-kappa B; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein