Sex Differences in Estrogen Receptor [alpha] and [beta] Levels and Activation Status in LPS-Stimulated Human Macrophages

Immune function, inflammation, and atherosclerosis display sex differences and are influenced by 17[beta]-estradiol through estrogen receptors subtypes ER[alpha] and ER[beta]. Male tissues express active ERs, but their possible involvement in inflammation in males has never been assessed. Macrophages express both ER[alpha] and ER[beta] 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 ER[alpha] and ER[beta] in blood monocytes-derived macrophages (MDMs) from men and women. MDMs were incubated with 100ng/ml LPS for 24h and used to evaluate ER[alpha], ER[beta], P-ER[alpha], p38, and P-p38 expression by Western Blotting. In basal conditions, ER[alpha] and ER[beta] were significantly higher in female MDMs than in male MDMs. LPS up-regulated ER[alpha] and ER[alpha] phosphorylation in both sexes, with a significantly higher effect observed in male MDMs, and down-regulated ER[beta] level only in female MDMs. p38 and P-p38 proteins, indicative of ER[beta] activity, did not show sex differences both in basal conditions and after LPS treatment. Finally, ER[alpha]/ER[beta] and P-ER[alpha]/ER[alpha] ratios were significantly higher in male MDMs than in female ones. Our data indicate, for the first time, that LPS affects ER[alpha] but not ER[beta] activation status. We identify a significant role of ER[alpha] in LPS-mediated inflammatory responses in MDMs, which represents an initial step in understanding the influence of sex in the relationship between LPS and ER[alpha]. J. Cell. Physiol. 232: 340-345, 2017. © 2016 Wiley Periodicals, Inc.