title: Genistein suppresses antigen-specific immune responses through competition with 17beta-estradiol for estrogen receptors in ovalbumin-immunized BALB/c mice.
abstract: OBJECTIVE
  The aim of this study was to determine the effects of phytoestrogen genistein on antigen (Ag)-specific immune responses and elucidate the mechanisms underlying those effects.
  
  
  METHODS
  Ovalbumin (OVA)-immunized BALB/c mice were administered genistein for 35 d, and OVA-specific immune responses were examined by measuring OVA-specific proliferative responses, production of cytokines, and antibody responses. To assess the effect of genistein on antibody responses to thymus-independent Ag, mice were immunized with 2,4,6-trinitrophenyl (TNP)-Ficoll instead of OVA. Effect of genistein on the functions of CD11c(+) dendritic cells was also examined. Finally, to determine the contribution of estrogen receptor to genistein-mediated immune regulation, mice that had been administered genistein were treated with the estrogen receptor antagonist ICI 182,780 and OVA-specific proliferative responses were examined.
  
  
  RESULTS
  OVA-specific proliferative responses and interferon-gamma production levels were decreased in mice administered 20 mg/kg genistein compared with those in control mice without reduction in responses to anti-CD3 monoclonal (m)antibody. The level of OVA-specific immunoglobulin (Ig)G1 was also decreased in mice administered genistein. Levels of OVA-specific IgG2a and IgG2b production and interleukin-4 production in response to OVA were not significantly different but tended to decrease in genistein-treated mice. Genistein administration did not influence the TNP-specific IgM and IgG levels. Furthermore, genistein did not affect the Ag-presenting activity of CD11c(+) dendritic cells. Treatment with ICI 182,780 decreased OVA-specific proliferative responses, but genistein did not suppress these responses synergistically in mice treated with ICI 182,780.
  
  
  CONCLUSIONS
  The results of this study suggest that genistein suppresses Ag-specific immune responses. The mechanism underlying the suppression is responsible for the competition of genistein with endogenous 17beta-estradiol for estrogen receptors.
authors.affiliation: Department of International Nutrition, Institution of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Kogiso
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakai
authors.forename: Kaori
authors.initials: K
authors.lastname: Mitsuya
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Komatsu
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D001667:Binding, Competitive; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D019833:Genistein / Q000378:metabolism / Q000494:pharmacology*; D007109:Immunity / Q000187:drug effects*; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D011960:Receptors, Estrogen / Q000378:metabolism*; D013154:Spleen / Q000166:cytology; D014301:Trinitrobenzenes / Q000276:immunology
chemical_list: D000941:Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011960:Receptors, Estrogen; C020529:TNP-ficoll; D014301:Trinitrobenzenes; D015847:Interleukin-4; D005362:Ficoll; D004958:Estradiol; D007371:Interferon-gamma; D010047:Ovalbumin; D019833:Genistein