ERα-mediated repression of pro-inflammatory cytokine expression by glucocorticoids reveals a crucial role for TNFα and IL1α in lumen formation and maintenance.
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 TNFα and IL1α in the formation and, more importantly, maintenance of a single central lumen. We also studied the mechanism by which glucocorticoids repress TNFα and IL1α expression. Interestingly, regulation of pro-inflammatory cytokine expression and subsequent lumen formation is mediated by estrogen receptor α (ERα) 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 ERα-regulated pro-inflammatory cytokine expression in lumen formation and maintenance.
Oncologic Pathology Group, Departamento de Ciències Mèdiques Bàsiques, Universitat de Lleida, Lleida, Spain.
Nuria
N
Eritja
Cristina
C
Mirantes
David
D
Llobet
Gemma
G
Masip
Xavier
X
Matias-Guiu
Xavi
X
Dolcet
D000818:Animals; D016764:Cell Polarity; D015536:Down-Regulation; D004717:Endometrium / Q000254:growth & development* / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
D047628:Estrogen Receptor alpha; D005938:Glucocorticoids; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D014409:Tumor Necrosis Factor-alpha