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

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 (5mg/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.
AuthorsEun Hwa Kang, Tae Young Kown, Goo Taeg Oh, Weung Feel Park, Sung-Il Park, Sung Kyu Park, Young Ik Lee
JournalAntiviral research (Antiviral Res) Vol. 72 Issue 2 Pg. 100-6 (Nov 2006) ISSN: 0166-3542 [Print] Netherlands
PMID16720052 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Hepatitis B Antibodies
  • Hepatitis B e Antigens
  • Immunologic Factors
  • Ellagic Acid
  • Interleukin-4
  • Interferon-gamma
Topics
  • Animals
  • B-Lymphocytes (immunology)
  • Cells, Cultured
  • Cytotoxicity Tests, Immunologic
  • Ellagic Acid (administration & dosage, pharmacology)
  • Hepatitis B Antibodies (biosynthesis, blood)
  • Hepatitis B e Antigens (immunology)
  • Hepatitis B virus (immunology)
  • Immune Tolerance (drug effects)
  • Immunologic Factors (pharmacology)
  • Interferon-gamma (biosynthesis)
  • Interleukin-4 (biosynthesis)
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Plants, Medicinal
  • T-Lymphocytes (immunology)
  • T-Lymphocytes, Cytotoxic (immunology)

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