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Background  Monocytes and macrophages are key innate immune effector cells that produce cytokines and chemokines upon activation. We and others have shown that 17β-estradiol (E2) has a direct role in the modulation of monocyte and macrophage immune function. However, relatively little is known about the ability of E2 to regulate isoform expression of estrogen receptors (ERs) in these cells.    Methodology/Principal Findings  In this study, we quantify expression of ERα and ERβ in human monocytes and macrophages. We also show for the first time that the N-terminal truncated ERα variant, ERα46, is expressed in both cell types. Promoter utilization studies reveal that transcription of ERα in both cell types occurs from upstream promoters E and F. Treatment with E2 induces ERα expression in macrophages but has no effect on ERβ levels in either cell type. During monocyte-to-macrophage differentiation, ERα is upregulated in a time-dependent manner. Previous studies by our group demonstrated that E2 treatment attenuates production of the chemokine CXCL8 in an ER-dependent manner. We now show that ERα expression levels parallel the ability of E2 to suppress CXCL8 production.    Conclusions/Significance  This work demonstrates for the first time that human macrophages predominantly express the truncated ER variant ERαp46, which is estradiol-inducible. This is mediated through usage of the ERα F promoter. Alternative promoter usage may account for tissue and cell type-specific differences in estradiol-induced effects on gene expression. These studies signify the importance of ERα expression and regulation in the ability of E2 to modulate innate immune responses.

Estradiol Regulates Expression of Estrogen Receptor ERα46 in Human Macrophages