Mechanisms of chorioamnionitis-associated preterm birth: interleukin-1β inhibits progesterone receptor expression in decidual cells

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-1 beta decreased PR expression and significantly increased PGE(2) and PGF(2 alpha). production and COX-2 expression. The addition of PGF(2 alpha) to DC cultures also suppressed PR expression. However, the COX inhibitor, indomethacin, did not reverse IL-1 beta suppression of PR expression in DC cultures. Although IL-1 beta treatment activated the NF-kappa B, 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-1 beta. These findings suggest that CAM-associated PTB is induced at least in part by IL-1 beta-mediated functional progesterone withdrawal. Copyright (C) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.