Interferon induces interleukin 8 and bone marrow stromal cell antigen 2 expression, inhibiting the production of hepatitis B virus surface antigen from human hepatocytes

Biochem Biophys Res Commun. 2017 May 6;486(3):858-863. doi: 10.1016/j.bbrc.2017.03.150. Epub 2017 Mar 28.

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.

Keywords: BST2; HBV; HBsAg; Interleukin 8.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Cell Line, Tumor
  • Chemokine CXCL10 / agonists*
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / immunology
  • GPI-Linked Proteins / agonists
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / immunology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genes, Reporter
  • Hep G2 Cells
  • Hepatitis B Surface Antigens / drug effects*
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B virus / genetics
  • Hepatitis B virus / pathogenicity
  • Host-Pathogen Interactions*
  • Humans
  • Interferon-alpha / pharmacology*
  • Interleukin-8 / agonists*
  • Interleukin-8 / genetics
  • Interleukin-8 / immunology
  • Luciferases / genetics
  • Luciferases / immunology
  • Poly I-C / genetics
  • Poly I-C / immunology
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology
  • Signal Transduction
  • Transfection

Substances

  • Antigens, CD
  • BST2 protein, human
  • CXCL10 protein, human
  • Chemokine CXCL10
  • GPI-Linked Proteins
  • Hepatitis B Surface Antigens
  • Interferon-alpha
  • Interleukin-8
  • RNA, Messenger
  • Luciferases
  • Poly I-C