title: [Toll-like receptor dependent innate immune responses by primary mouse hepatocytes and its control of  HBV replication].
abstract: OBJECTIVE
  This report aims to investigate the Toll-like receptor (TLR) signaling pathways and induced antiviral activity in hepatocytes.
  
  
  METHODS
  We isolated primary hepatocytes from wild-type C57BL/6 mice and examined the expression of TLR by realtime RT-PCR. Hepatocytes were stimulated with TLR 1-9 agonists and the supernatants were harvested. The secretion of cytokines were tested by ELISA. The antiviral effectors in supernatants were assayed via virus protection assay (in EMCV system) and the control of HBV replication were assessed via Southern blotting (in HBV system).
  
  
  RESULTS
  We demonstrated that hepatocytes expressed TLR1-9. In accordance with these TLR expression profiles, hepatocytes responded to all TLR ligands by producing inflammatory cytokines (TNF-α or IL-6), to TLR -1,-3,-7 and -9 ligands by producing type I IFN (IFN-α or IFN-β). Only TLR 3 and TLR 7 agonists could stimulate the production of high amounts of antiviral mediators by hepatocytes in virus protection assay. By contrast, supernatants from TLR1, -3 and -4 directly stimulated hepatocytes and TLR 3, -7 and -9 transfected hepatocytes were able to potently suppress HBV replication.
  
  
  CONCLUSIONS
  Primary hepatocytes display a unique TLR signaling pathway and can control HBV replication after stimulation by TLR agonists in mice. It may be helpful for the development of TLR-based therapeutic approaches against hepatotropic virus.
authors.affiliation: Division of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Ming-fa
authors.initials: MF
authors.lastname: Chen
authors.forename: You-chen
authors.initials: YC
authors.lastname: Xia
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Chan
authors.initials: C
authors.lastname: Sun
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Shen-pei
authors.initials: SP
authors.lastname: Liu
authors.forename: You-hua
authors.initials: YH
authors.lastname: Hao
authors.forename: Meng-ji
authors.initials: MJ
authors.lastname: Lu
authors.forename: Jörg F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: Dong-liang
authors.initials: DL
authors.lastname: Yang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006515:Hepatitis B virus / Q000276:immunology / Q000502:physiology*; D022781:Hepatocytes / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D051193:Toll-Like Receptors