title: Caspase-1-mediated cytokine release from gestational tissues, placental, and cord blood.
abstract: Distinguishing between fetal and maternal inflammatory responses is necessary for understanding the immune interplay either side of the placenta. Fetal immunity reaches maturity during extrauterine life and while basic inflammatory responses afford a certain degree of protection, fetuses are vulnerable to infection. With the discovery of inflammasomes-intracellular scaffolds that facilitate the elaboration of reactions resulting in the release of mature interleukin-1β (IL-1β)-it is necessary to consider how inflammatory stimuli are processed. The purinergic P2X7 receptor located on haematopoietic cells is a key intermediary in signal transduction initiated at Toll-like receptors (TLR) terminating in release of the mature IL-1β product. We demonstrate herein that IL-1β release from fetal membranes and mononuclear cells isolated from cord, placental, and maternal blood, obtained at term, is P2X7- and caspase-1 dependent. The P2X7-dependent release of the cytokine, which was highest from choriodecidua, was attenuated by progesterone (P4), prolactin and an NFkB inhibitor. The NLRP3 inflammasome appears necessary for the processing of IL-1β in gestational tissues and leukocytes.
authors.affiliation: Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, The Royal Derby Hospital, University of Nottingham Derby, UK.
authors.forename: Ebtehaj
authors.initials: E
authors.lastname: Maneta
authors.affiliation: Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, The Royal Derby Hospital, University of Nottingham Derby, UK.
authors.forename: Averil Y
authors.initials: AY
authors.lastname: Warren
authors.affiliation: Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, The Royal Derby Hospital, University of Nottingham Derby, UK.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Hay
authors.affiliation: Division of Medical Sciences and Graduate Entry Medicine, School of Medicine, The Royal Derby Hospital, University of Nottingham Derby, UK.
authors.forename: Raheela N
authors.initials: RN
authors.lastname: Khan
keywords: IL-1β; P2X7 receptor; caspase-1; inflammasome; parturition; pregnancy