title: Sex Differences in Estrogen Receptor α and β Levels and Activation Status in LPS-Stimulated Human Macrophages.
abstract: Immune function, inflammation, and atherosclerosis display sex differences and are influenced by 17β-estradiol through estrogen receptors subtypes ERα and ERβ. Male tissues express active ERs, but their possible involvement in inflammation in males has never been assessed. Macrophages express both ERα and ERβ and offer the opportunity to evaluate the role of ER levels and activation in inflammation. We assessed the ability of lipopolysaccharide (LPS) to modulate, in a sex-specific way, the expression and the activation status of ERα and ERβ in blood monocytes-derived macrophages (MDMs) from men and women. MDMs were incubated with 100 ng/ml LPS for 24 h and used to evaluate ERα, ERβ, P-ERα, p38, and P-p38 expression by Western Blotting. In basal conditions, ERα and ERβ were significantly higher in female MDMs than in male MDMs. LPS up-regulated ERα and ERα phosphorylation in both sexes, with a significantly higher effect observed in male MDMs, and down-regulated ERβ level only in female MDMs. p38 and P-p38 proteins, indicative of ERβ activity, did not show sex differences both in basal conditions and after LPS treatment. Finally, ERα/ERβ and P-ERα/ERα ratios were significantly higher in male MDMs than in female ones. Our data indicate, for the first time, that LPS affects ERα but not ERβ activation status. We identify a significant role of ERα in LPS-mediated inflammatory responses in MDMs, which represents an initial step in understanding the influence of sex in the relationship between LPS and ERα. J. Cell. Physiol. 232: 340-345, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy. ilacampesi79@yahoo.it.|Laboratory of Sex-Gender Medicine, National Institute of Biostructures and Biosystems, Osilo, Italy. ilacampesi79@yahoo.it.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Campesi
authors.affiliation: Cell Physiology Lab, Department of Science, University Roma Tre, Rome, Italy. maria.marino@uniroma3.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Marino
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Montella
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Pais
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.|Assessorato alle Politiche per la Persona of Basilicata Region, Potenza, Italy.
authors.forename: Flavia
authors.initials: F
authors.lastname: Franconi
mesh_terms: D000328:Adult; D015153:Blotting, Western; D003720:Densitometry; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000166:cytology*; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008070:Lipopolysaccharides