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Showing papers by "Dennis B. Lubahn published in 2005"


Journal ArticleDOI
TL;DR: The results demonstrate that ERα deficiency in splenic macrophages, but not CD11c+ splenic dendritic cells pulsed with OVA significantly enhances proliferative responses and IFN-γ production by transgenic OVA peptide-specific CD4+ T cells when compared with Ag-pulsed APC from wild-type littermates.
Abstract: The effects of 17beta-estradiol (E2) on immune function have been extensively reported. The effects are dependent on concentration and duration of exposure and potential differences in signaling between the known E2 receptors, estrogen receptors (ER) alpha and ERbeta. Through the use of ER-deficient mice, we and others have begun to demonstrate the role of the two known receptors in modulating immune functional activities. Previous studies have shown that cells of the innate immune system have altered function (bactericidal capacity) and patterns of cytokine expression (increased proinflammatory cytokine expression) through amelioration of ERalpha signaling. In this study, we extend these studies to analysis of T cell differentiation and proliferation in APC-dependent and APC-independent in vitro assay systems. Our results demonstrate that ERalpha deficiency in splenic macrophages, but not CD11c+ splenic dendritic cells pulsed with OVA significantly enhances proliferative responses and IFN-gamma production by transgenic OVA peptide-specific (OT-II) CD4+ T cells when compared with Ag-pulsed APC from wild-type littermates. The addition of E2 in this culture system did not significantly affect the production of IFN-gamma. In addition, when purified CD4+ T cells from ERalpha-deficient and wild-type littermates were stimulated with anti-CD3/CD28 Ab in the absence of E2, there were no significant differences in IFN-gamma or IL-4 production. However, the addition of E2 significantly increased IL-4 secretion, as well as increased GATA-3 mRNA levels from ERalpha-replete CD4+ T cells, while this effect was abrogated in ERalpha-deficient CD4+ T cells.

128 citations


Journal ArticleDOI
TL;DR: Repression of Nrf2-mediated transcription by E2-bound ERα provides a potential drug-screening target for the development of selective estrogen receptor modulators with a lower risk of causing cancer.

71 citations


Journal ArticleDOI
TL;DR: The data suggest that ERalpha plays an important role in the mammary gland development as well as in the induction of mammary hyperplasia in aromatase transgenic mice, suggesting estrogen/ERalpha-mediated actions are critical for mammary development and carcinogenesis.

35 citations


Journal ArticleDOI
TL;DR: The present data suggest that in females lacking ERalpha, ANG II causes blunting of cardiac baroreflexes similar to males and may be indicative of a direct modulatory effect of the ERalpha on those central mechanisms involved in ANG II-induced resetting of heart rates.
Abstract: Estrogen facilitates baroreflex heart rate responses evoked by intravenous infusion of ANG II and phenylephrine (PE) in ovariectomized female mice. The present study aims to identify the estrogen r...

29 citations