Sex Differences in Estrogen Receptor and Levels and Activation Status in LPS-Stimulated Human Macrophages

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