Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis.
Details
Serval ID
serval:BIB_87ADFD6D82E4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Macrophage migration inhibitory factor is involved in a positive feedback loop increasing aromatase expression in endometriosis.
Journal
American Journal of Pathology
ISSN
1525-2191 (Electronic)
ISSN-L
0002-9440
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
181
Number
3
Pages
917-927
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
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
Create date
01/11/2012 18:40
Last modification date
20/08/2019 14:46