Lipoxin A4 is a novel estrogen receptor modulator.

Détails

ID Serval
serval:BIB_1738B08D01AB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Lipoxin A4 is a novel estrogen receptor modulator.
Périodique
Faseb Journal
Auteur(s)
Russell R., Gori I., Pellegrini C., Kumar R., Achtari C., Canny G.O.
ISSN
1530-6860 (Electronic)
ISSN-L
0892-6638
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
25
Numéro
12
Pages
4326-4337
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Inflammation is intimately linked with naturally occurring remodeling events in the endometrium. Lipoxins comprise a group of short-lived, nonclassic eicosanoids possessing potent anti-inflammatory and proresolution properties. In the present study, we investigated the role of lipoxin A(4) (LXA(4)) in the endometrium and demonstrated that 15-LOX-2, an enzyme necessary for LX biosynthesis, is expressed in this tissue. Our results establish that LXA(4) possesses robust estrogenic activity through its capacity to alter ERE transcriptional activity, as well as expression of estrogen-regulated genes, alkaline phosphatase activity, and proliferation in human endometrial epithelial cells. Interestingly, LXA(4) also demonstrated antiestrogenic potential, significantly attenuating E2-induced activity. This estrogenic activity was directly mediated through estrogen receptors (ERs). Subsequent investigations determined that the actions of LXA(4) are exclusively mediated through ERα and closely mimic those of the potent estrogen 17β-estradiol (E2). In binding assays, LXA(4) competed with E2 for ER binding, with an IC(50) of 46 nM. Furthermore, LXA(4) exhibited estrogenic activity in vivo, increasing uterine wet weight and modulating E2-regulated gene expression. These findings reveal a previously unappreciated facet of LXA(4) bioactions, implicating this lipid mediator in novel immunoendocrine crosstalk mechanisms.
Mots-clé
Alkaline Phosphatase/metabolism, Arachidonate 15-Lipoxygenase/metabolism, Base Sequence, Binding, Competitive, Cell Line, Cell Proliferation/drug effects, Endometrium/cytology, Endometrium/drug effects, Epithelial Cells/cytology, Epithelial Cells/drug effects, Estradiol/metabolism, Estrogen Receptor Modulators/metabolism, Estrogen Receptor Modulators/pharmacology, Estrogen Receptor alpha/antagonists & inhibitors, Estrogen Receptor alpha/genetics, Female, Humans, Lipoxins/metabolism, Lipoxins/pharmacology, RNA, Messenger/genetics, RNA, Messenger/metabolism, RNA, Small Interfering/genetics, Receptors, Aryl Hydrocarbon/antagonists & inhibitors, Receptors, Aryl Hydrocarbon/genetics, Receptors, Formyl Peptide/antagonists & inhibitors, Receptors, Formyl Peptide/genetics, Receptors, Lipoxin/antagonists & inhibitors, Receptors, Lipoxin/genetics, Signal Transduction
Pubmed
Web of science
Création de la notice
08/09/2011 16:06
Dernière modification de la notice
20/08/2019 12:47
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