The flavonoid ellagic acid from a medicinal herb inhibits host immune tolerance induced by the hepatitis B virus-e antigen

Eun Hwa Kang, Tae Young Kown, Goo Taeg Oh, Weung Feel Park, Sung Il Park, Sung Kyu Park, Young Ik Lee

Research output: Contribution to journalArticlepeer-review

65 Scopus citations

Abstract

The aim of this study is to characterize the role of ellagic acid, a flavonoid from a medicinal herb which blocks HBeAg secretion in a HBV infected cell line and in HBeAg transgenic mice, in immune tolerance in chronic HBV infection. Using the mouse strain C57ML/6, HBeAg-producing transgenic mice (HBeAg-Tg), under the control of metal ion-inducible promoter were generated. The effect on immune tolerance of HBeAg-Tg and the release of immune tolerance by the inhibitor of HBeAg secretion, ellagic acid, was tested using T/B cell proliferation, HBeAg/HBeAb production, cytotoxic T-lymphocyte (CTL) and cytokine assays. C57ML/6 based HBeAg-producing HBeAg-Tg mice were tolerant to HBeAg at the T and B-cell level, did not produce antibodies to HBeAg in vivo and in vitro, produced minimal levels of cytokines (IL-4 and IFN-gamma) and decreased CTL responses, while feeding mice with ellagic acid (5 mg/kg body weight) blocked the immune tolerance caused by HBeAg. Our results suggest that host immune tolerance induced by HBeAg during HBV infection, a viral strategy to guarantee HBV infection, can be overcome by ellagic acid, thus it can be used as a therapeutic for HBV-carriers.

Original languageEnglish
Pages (from-to)100-106
Number of pages7
JournalAntiviral Research
Volume72
Issue number2
DOIs
StatePublished - Nov 2006

Bibliographical note

Funding Information:
This study was supported by Korea Science and Engineering Foundation Grants (Science Research Center Fund, R11-2000-080-09002-0 and R02-2003-000-10070-0) and KRIBB Research Initiative Program Fund (KGS0520513).

Keywords

  • Anti-HBV infection
  • Ellagic acid
  • Hepatitis B virus-e antigen
  • Immune tolerance

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