title: Interferon induces interleukin 8 and bone marrow stromal cell antigen 2 expression, inhibiting the production of hepatitis B virus surface antigen from human hepatocytes.
abstract: Hepatitis B virus (HBV) surface antigen (HBsAg) loss is one of the treatment goals of chronic HBV infection. Bone marrow stromal cell antigen 2 (BST2) is one of the interferon (IFN)-stimulated genes (ISGs) and inhibits the release of various enveloped viruses. Here we examined the effects of antiviral treatment on HBsAg levels and its intracellular mechanism in HBsAg-producing hepatocytes. In PLC/PRF/5 and Huh1, IFNα-2a treatment decreased HBsAg levels in their conditioned media. Upregulation of interleukin 8 (IL8), toll-like receptor 2 (TLR2) and interferon gamma-induced protein 10 (IP10) mRNAs was associated with the reduction of HBsAg in both PLC/PRF/5 and Huh1. The HBsAg level was upregulated by knockdown of IL8, TLR2 or IP10. Exogenous addition of IL8 enhanced BST2 promoter activity and BST2 mRNA expression. Additionally, knockdown of IL8 could lead to the downregulation of BST2 mRNA. Transfection of poly(I-C) enhanced IL8 and BST2 mRNA expression and inhibited HBsAg secretion from PLC/PRF/5 cells. In conclusion, IL8 might play an important role in the enhancement of BST2 and be involved in HBsAg eradication.
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Haga
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan. Electronic address: kandat-cib@umin.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kanda
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan; Department of Molecular Virology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamoto
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Reina
authors.initials: R
authors.lastname: Sasaki
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Shuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokosuka
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D058851:GPI-Linked Proteins / Q000819:agonists / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016209:Interleukin-8 / Q000819:agonists* / Q000235:genetics / Q000276:immunology; D008156:Luciferases / Q000235:genetics / Q000276:immunology; D011070:Poly I-C / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014162:Transfection; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D054357:Chemokine CXCL10; D058851:GPI-Linked Proteins; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D016209:Interleukin-8; D008156:Luciferases; D011070:Poly I-C; D012333:RNA, Messenger; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C114753:CXCL10 protein, human
keywords: BST2; HBV; HBsAg; Interleukin 8