Estrogen receptor-α deficiency promotes increased TNF-α secretion and bacterial killing by murine macrophages in response to microbial stimuli in vitro

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Abstract
In this series of studies, we determined the potential role of intracellular estrogen receptors (ER), ERα and ERβ, on macrophage function in response to bacterial stimuli. The sex hormone 17β-estradiol (E2) and ER have been shown to modulate inflammatory responses as well as T helper cell type 1 (TH1)/TH2 responses. The mechanisms E2 and its receptors use to alter these immune functions remain largely unknown. ERα and ERβ possess complex actions in tissues where they are expressed. We have characterized the receptor repertoire of murine dendritic cells and thioglycollate-elicited peritoneal macrophages (PM). Both cell types express mRNA for ERα. Neither cell type expressed detectable amounts of ERβ mRNA, as determined by reverse transcriptase-polymerase chain reaction using exon-specific primers spanning each of the seven intron/exon junctions. Primary macrophages from ERα- and ERβ-deficient severe combined immunodeficiency mice [ERα knockout (KO) and ERßKO, respectively] were used to delineate the effects and potential mechanisms via which steroid receptors modulate macrophage function. ERα-deficient PM exposed ex vivo to lipopolysaccharide or Mycobacterium avium exhibited significant increases in tumor necrosis factor α (TNF-α) secretion as well as reduction in bacterial load when compared with wild-type (WT) PM. In contrast, ERβ-deficient PM possessed no significant difference in TNF-α secretion or in bacterial load when compared with WT littermates. These studies suggest that ERα, but not ERβ, modulates murine PM function.
Funding Information
  • The University of Missouri Center for Phytonutrient and Phytochemical Research (NIEHS P01 ES10535)