title: Regulation of the endothelin/endothelin receptor system by interleukin-1{beta} in human myometrial cells.
abstract: Proinflammatory cytokines produced at the fetomaternal interface, such as IL-1beta, have been implicated in preterm and term labor. The present study was performed to evaluate the influence of IL-1beta on the endothelin (ET)/ET receptor system in human myometrial cells. We report that myometrial cells under basal conditions not only respond to but also secrete ET-1, one of the main regulators of uterine contractions. Prolonged exposure of the cells to IL-1beta led to a decrease in prepro-ET-1 and ET-3 mRNA correlated with a decrease in immunoreactive ET-1 and ET-3 levels in the culture medium. Whereas ETA receptor expression at both protein and mRNA levels was not affected by IL-1beta treatment, we demonstrated an unexpected predominance of the ETB receptor subtype under this inflammatory condition. Whereas the physiological function of ETB remains unclear, we confirmed that only ETA receptors mediate ET-1-induced myometrial cell contractions under basal conditions. By contrast, prolonged exposure of the cells to IL-1beta abolished the contractile effect induced by ET-1. Such a regulation of IL-1beta on the ET release and the balance of ETA to ETB receptors leading to a loss of ET-1-induced myometrial cell contractions suggest that complex regulatory mechanisms take place to constraint the onset of infection-induced premature contractions.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 427 Paris, F-75270 cedex 06 France. breuiller-fouche@cochin.inserm.fr
authors.forename: Michelle
authors.initials: M
authors.lastname: Breuiller-Fouché
authors.forename: Catherine
authors.initials: C
authors.lastname: Morinière
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Dallot
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Oger
authors.forename: Régis
authors.initials: R
authors.lastname: Rebourcet
authors.forename: Dominique
authors.initials: D
authors.lastname: Cabrol
authors.forename: Marie-Josèphe
authors.initials: MJ
authors.lastname: Leroy
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects / Q000502:physiology; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D009215:Myometrium / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000235:genetics / Q000378:metabolism; D017466:Receptors, Endothelin / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D007375:Interleukin-1; D020033:Protein Isoforms; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D003094:Collagen