ERα-mediated repression of pro-inflammatory cytokine expression by glucocorticoids reveals a critical role for TNFα and IL1α in lumen formation and maintenance.

Abstract

SummaryMost glandular tissues comprise polarized epithelial cells organized around a single central lumen. Although there is active research investigating the molecular networks involved in the regulation of lumenogenesis, little is known about the extracellular factors that influence lumen formation and maintenance. Using a three-dimensional culture system of epithelial endometrial cells, we have revealed a new role for pro-inflammatory cytokines such as TNFa and IL1a in the formation and, more importantly, maintenance of a single central lumen. We also studied the mechanism by which glucocorticoids repress TNFa and IL1a expression. Interestingly, regulation of pro-inflammatory cytokine expression and subsequent lumen formation is mediated by estrogen receptor a (ERa) but not by the glucocorticoid receptor. Finally, we investigated the signaling pathways involved in the regulation of lumen formation by proinflammatory cytokines. Our results demonstrate that activation of the ERK/MAPK signaling pathway, but not the PI3K/Akt signaling pathway, is important for the formation and maintenance of a single central lumen. In summary, our results suggest a novel role for ERaregulated pro-inflammatory cytokine expression in lumen formation and maintenance.

A combination of lactic acid bacteria regulates Escherichia coli infection and inflammation of the bovine endometrium

“…Our ultrastructural findings are relevant because mitochondrial damage and cell death compromise the tridimensional organization of epithelial cells and hampers their barrier function, which is crucial for endometrium homeostasis (Bryant and Mostov, 2008). These results complemented our biochemical data because intracellular signaling pathways of inflammation actively participate in tissue homeostasis (Eritja et al, 2012) and may induce morphological changes (Saito et al, 2014).…”

Gene expression of estrogen receptor-alpha in orbital fibroblasts in Graves’ ophthalmopathy

“…demonstrated that a selective ERA antagonist reverses the anti-inflammatory activity exhibited by DEX, suggesting that the anti-inflammatory effect of DEX requires the participation of ER (20). Additionally, study performed with mice endometrial cells observed that the suppression of pro-inflammatory cytokines expression by glucocorticoids was mediated through ERA and not through GR, as it would be expected (9). In our study, ERA gene expression was modulated according to glucocorticoid …”

“…Experimental studies have suggested that estradiol interferes with PPARG action and, consequently, with adipogenesis, by inhibiting adipocytic differentiation (7). Moreover, the relation between ER and inflammation has been described (5,8), with evidence that the regulation of pro-inflammatory cytokines expression by corticosteroids might be mediated by ERA and not by glucocorticoid receptor (GR) (9). These reports reinforce the hypothesis that ER, and particularly ERA, influences GO pathogenesis.…”

An expandable donor-free supply of functional hepatocytes for toxicology

“…Recent work has demonstrated that B-13 cells are capable of differentiating into ductal-like cells 87 and that an alternative nuclear receptorthe oestrogen receptor-α (ERα)mediates the effects of glucocorticoids in lumen-forming cells (such as the progenitor cells of the liver, which are bi-potential and capable of forming hepatocytes or the lumen-forming cholangiocytes). 132 A, demonstrates that the mRNA for ERα as well as the related ER gene ERβ are not detectable in B-13 cells in contrast to rat hepatocytes (which are known to express ERα 133 ) and uterus and the ovary (which has previously been reported to express the ERβ 134 ). RT-PCR analysis for the expression of ERα and ERβ mRNA transcripts in 4 separate B-13 cell cultures, after 30 cycles essentially as described.…”