Genistein suppresses antigen-specific immune responses through competition with 17β-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-γ 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 17β-estradiol for estrogen receptors.