Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis.

Détails

ID Serval
serval:BIB_87ADFD6D82E4
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis.
Périodique
American Journal of Pathology
Auteur(s)
Veillat V., Sengers V., Metz C.N., Roger T., Leboeuf M., Mailloux J., Akoum A.
ISSN
1525-2191 (Electronic)
ISSN-L
0002-9440
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
181
Numéro
3
Pages
917-927
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Résumé
Immune-endocrine interplay may play a major role in the pathogenesis of endometriosis. In the present study, we have investigated the interaction between macrophage migration inhibitory factor (MIF), a major pro-inflammatory and growth-promoting factor markedly expressed in active endometriotic lesions, and estradiol (E(2)) in ectopic endometrial cells. Our data showed a significant increase of MIF protein secretion and mRNA expression in endometriotic cells in response to E(2). MIF production was blocked by Fulvestrant, an estrogen receptor (ER) antagonist, and induced by ERα and ERβ selective agonists propyl-pyrazole-triol (PPT) and diarylpropionrile (DPN), respectively, thus demonstrating a specific receptor-mediated effect. Cell transfection with MIF promoter construct showed that E(2) significantly stimulates MIF promoter activity. Interestingly, our data further revealed that MIF reciprocally stimulates aromatase protein and mRNA expression via a posttranscriptional mRNA stabilization mechanism, that E(2) itself can upregulate aromatase expression, and that inhibition of endogenous MIF, using MIF specific siRNA, significantly inhibits E(2)-induced aromatase. Thus, the present study revealed the existence of a local positive feedback loop by which estrogen acts directly on ectopic endometrial cells to upregulate the expression of MIF, which, in turn, displays the capability of inducing the expression of aromatase, the key and rate-limiting enzyme for estrogen synthesis. Such interplay may have a considerable impact on the development of endometriosis.
Pubmed
Web of science
Création de la notice
01/11/2012 19:40
Dernière modification de la notice
20/08/2019 15:46
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