Estradiol can enhance both cell-med

Estradiol can enhance both cell-mediated and humoral immune responses (Straub, 2007). Generally, low E2 concentrations promote Th1 responses and cell-mediated immunity and high concentrations of E2 augment Th2 responses and humoral immunity (Straub, 2007). The binding of E2 to the ER increases Ifnγtranscription by interacting with estrogen response elements in the promoter region of the Ifnγ gene (Fox et al., 1991). Low dose E2 also upregulates mitogen activated protein kinase (MAPK), T-bet, and select microRNAs to increase production of IFN-γ by T cells, which can be reversed by treatment of cells with the ER antagonist ICI 182,780 (Dai et al., 2008; Karpuzoglu et al., 2007; Suzuki et al., 2008). Estradiol regulates proinflammatory responses that are transcriptionally mediated by NF-κB (Dai et al., 2007).