title: Mechanisms of chorioamnionitis-associated preterm birth: interleukin-1β inhibits progesterone receptor expression in decidual cells.
abstract: In chorioamnionitis (CAM), a major cause of preterm birth (PTB), maternal-fetal inflammation of the decidua and amniochorion cause the release of cytokines that elicit cervical ripening, fetal membrane rupture and myometrial activation. We posit that this inflammatory milieu triggers PTB by inhibiting progesterone receptor (PR) expression and increasing decidual prostaglandin (PG) production. Immunohistochemical staining of decidua detected significantly lower PR levels in decidual cells (DCs) from CAM-complicated PTB. Incubation of DCs with IL-1β decreased PR expression and significantly increased PGE2 and PGF2α production and COX-2 expression. The addition of PGF2α to DC cultures also suppressed PR expression. However, the COX inhibitor, indomethacin, did not reverse IL-1β suppression of PR expression in DC cultures. Although IL-1β treatment activated the NF-KB, ERK1/2 and p38 MAPK signalling cascades in DCs, inhibition of ERK1/2 MAPK signalling alone was sufficient to completely reverse the suppression of PR levels by IL-1β. These findings suggest that CAM-associated PTB is induced at least in part by IL-1β-mediated functional progesterone withdrawal.
authors.affiliation: Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Guzeloglu-Kayisli
authors.affiliation: Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Umit A
authors.initials: UA
authors.lastname: Kayisli
authors.affiliation: Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Nihan
authors.initials: N
authors.lastname: Semerci
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Murat
authors.initials: M
authors.lastname: Basar
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Lynn F
authors.initials: LF
authors.lastname: Buchwalder
authors.affiliation: Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
authors.affiliation: Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH, USA.|Center for Perinatal Research, Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
authors.affiliation: Department of Human Pathology and Oncology, University of Siena, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Arcuri
authors.affiliation: Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Kellie
authors.initials: K
authors.lastname: Larsen
authors.affiliation: Department of Obstetrics and Gynecology, Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Frederick
authors.initials: F
authors.lastname: Schatz
authors.affiliation: Department of Obstetrics and Gynecology, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lockwood
mesh_terms: D002821:Chorioamnionitis / Q000378:metabolism*; D003656:Decidua / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D047928:Premature Birth / Q000209:etiology*; D060888:Real-Time Polymerase Chain Reaction; D011980:Receptors, Progesterone / Q000096:biosynthesis*
chemical_list: D053583:Interleukin-1beta; D011980:Receptors, Progesterone
keywords: IL-1β; chorioamnionitis; preterm birth; progesterone receptor