title: Role of the exogenous HCV core protein in the interaction of human hepatocyte proliferation and macrophage sub-populations.
abstract: BACKGROUND
  The core protein of hepatitis C virus (HCV) is found in the cytoplasm and nuclei of infected cells, including hepatocytes and other cells in the liver. The core protein could be secreted as well. Resident liver macrophages are dependent on the tissue micro-environment and external stimuli to differentiate M1 and M2 hypotypes with distinct functions, and increased expression of the nuclear transcription factor STAT3 was seen in M2-polarized macrophages. In contrast to proinflammatory M1 macrophages, M2 macrophages serve beneficial roles in chronic inflammation, immunosuppression, and tumorigenesis.
  
  
  METHODS
  Monocyte-derived human macrophage line (mTHP-1) was treated with the exogenous HCV core protein. Next, the mTHP-1 culture supernatant or cell pellets were added to culture media of normal human liver cell line (L02).
  
  
  RESULTS
  Only the culture supernatant stimulated L02 cells proliferation, which was associated with phosphorylated ERK expression. Core protein activated mTHP-1 cells showed enhanced pro- and anti-inflammatory cytokines secretion, which was accompanied by high expression of phosphorylated NF-κB105 and NF-κB65. However, phosphorylated STAT1, and STAT3, which are normally associated with M1 and M2 macrophage polarization, and cell surface expression of CD206, CD14, CD16, and CD86, were unaltered. A transwell co-culture system showed that only in mTHP-1 co-cultured with L02 in the presence of exogenous core protein, were higher levels of phosphorylated STAT3 and CD206 seen.
  
  
  CONCLUSIONS
  We showed L02 cells proliferation was accelerated by the culture supernatant of mTHP-1 cells treated with the exogenous HCV core protein. The exogenous core protein mediated the interaction between macrophages and hepatocytes in co-culture, which enhanced the expression of phosphorylated STAT3 and CD206 in macrophages.
authors.affiliation: Department of Immunology, Hebei Medical University, Shijiazhuang, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China.
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Department of Immunology, Hebei Medical University, Shijiazhuang, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Immunology, Hebei Medical University, Shijiazhuang, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China.
authors.forename: Shiru
authors.initials: S
authors.lastname: Cao
authors.affiliation: Department of Immunology, Hebei Medical University, Shijiazhuang, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China.
authors.forename: Wenzhang
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of Immunology, Hebei Medical University, Shijiazhuang, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China.
authors.forename: Wenran
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Immunology, Hebei Medical University, Shijiazhuang, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Immunology, Hebei Medical University, Shijiazhuang, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China.
authors.forename: Zhengzheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Hebei Medical University, Shijiazhuang, China; Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wei
mesh_terms: D051940:B7-2 Antigen / Q000096:biosynthesis; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000096:biosynthesis; D016174:Hepacivirus / Q000235:genetics; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000096:biosynthesis; D052002:NF-kappa B p50 Subunit / Q000096:biosynthesis; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D017452:Receptors, IgG / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000096:biosynthesis / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000378:metabolism; D051996:Transcription Factor RelA / Q000096:biosynthesis; D014758:Viral Core Proteins / Q000494:pharmacology*
chemical_list: D051940:B7-2 Antigen; C497964:CD86 protein, human; D017077:Culture Media, Conditioned; D016207:Cytokines; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D037181:Lectins, C-Type; D018950:Lipopolysaccharide Receptors; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D052002:NF-kappa B p50 Subunit; C498143:RELA protein, human; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051996:Transcription Factor RelA; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus