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

First Author  Eritja N Year  2012
Journal  J Cell Sci Volume  125
Issue  Pt 8 Pages  1929-44
PubMed ID  22328525 Mgi Jnum  J:197293
Mgi Id  MGI:5492015 Doi  10.1242/jcs.095067
Citation  Eritja N, et al. (2012) ERalpha-mediated repression of pro-inflammatory cytokine expression by glucocorticoids reveals a crucial role for TNFalpha and IL1alpha in lumen formation and maintenance. J Cell Sci 125(Pt 8):1929-44
abstractText  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 TNFalpha and IL1alpha in the formation and, more importantly, maintenance of a single central lumen. We also studied the mechanism by which glucocorticoids repress TNFalpha and IL1alpha expression. Interestingly, regulation of pro-inflammatory cytokine expression and subsequent lumen formation is mediated by estrogen receptor alpha (ERalpha) 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 ERalpha-regulated pro-inflammatory cytokine expression in lumen formation and maintenance.
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