The flavonoid ellagic acid from a medicinal herb inhibits host immune tolerance induced by the hepatitis B virus-e antigen.
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.
Kang
Eun Hwa
EH
Liver Cell Signal Transduction Lab, Taejon, Republic of Korea.
Kown
Tae Young
TY
Oh
Goo Taeg
GT
Park
Weung Feel
WF
Park
Sung-Il
SI
Park
Sung Kyu
SK
Lee
Young Ik
YI
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D004610:Ellagic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D006510:Hepatitis B Antibodies / Q000096:biosynthesis / Q000097:blood; D006513:Hepatitis B e Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects*; D007155:Immunologic Factors / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D010946:Plants, Medicinal; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D007155:Immunologic Factors; D004610:Ellagic Acid; D015847:Interleukin-4; D007371:Interferon-gamma