ER alpha-mediated repression of pro-inflammatory cytokine expression by glucocorticoids reveals a crucial role for TNF alpha and IL1 alpha in lumen formation and maintenance
Mirantes Barbeito, Cristina
Llobet Navàs, David
Masip Vilà, Gemma
MetadataShow full item record
Most 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 TNF alpha and IL1 alpha in the formation and, more importantly, maintenance of a single central lumen. We also studied the mechanism by which glucocorticoids repress TNF alpha and IL1 alpha expression. Interestingly, regulation of pro-inflammatory cytokine expression and subsequent lumen formation is mediated by estrogen receptor alpha (ER alpha) but not by the glucocorticoid receptor. Finally, we investigated the signaling pathways involved in the regulation of lumen formation by pro-inflammatory 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 ER alpha-regulated pro-inflammatory cytokine expression in lumen formation and maintenance.