Estrogenic compounds suppressed interferon-gamma production in mouse splenocytes through direct cell-cell interaction

Here, we reported the effects of 17β-estradiol (E2), isoflavone genistein (Gen), and daidzein (Dai) on the production of interferon (IFN)-γ by splenocytes isolated from C57BL/6N mice. When mouse splenocytes were stimulated with lipopolysaccharide, E2, Gen, and Dai suppressed the production of IFN-γ. However, when only nonadherent cell populations of splenocytes were tested, none of these estrogenic compounds suppressed IFN-γ production. This result indicates that IFN-γ production by nonadherent cell populations of splenocytes treated with estrogens is regulated by adherent cell populations. Moreover, direct cell-cell interaction between both populations was necessary for suppression of IFN-γ production by nonadherent populations. In addition, E2 conjugated with bovine serum albumin inhibited IFN-γ production as well as E2. This result suggests that the plasma membrane-associated estrogen receptor plays a prominent role in this suppression mechanism.