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.

NLRP3 Inflammasome Mediated Production of Th1/Th17 Cytokines in Response to Inflammatory Stimulants in Innate Immune Cells

“…It was reported that the ability of CBMCs to secrete IL-1β is dependent on a high CD14-expressing monocyte subset producing pro-1L-1β but characterized by impaired release of IL-1β attributed to low expression of NLRP3;P2X7 and pro-caspase-1 expression when compared to adult levels due to gestational agedependent immaturity of signal transduction pathways. [32,33] In accordance with previous report we also found low expression of NLRP3, caspase-1 and IL-1β production in neonatal cells when compared to adult cells.…”

Role of leucocyte caspase-1 activity in epidural-related maternal fever: a single-centre, observational, mechanistic cohort study

“…Mechanistically, assessing circulating leucocytes was an accessible first step, but the impact of bupivacaine on caspase-1-mediated cytokine release from leucocytes that accumulate in gestational tissues and the placenta may be more substantial during established labour. 38 Finally, we appreciate that modes of analgesia may be difficult to compare owing to the fact that women choosing epidural analgesia may experience more painful, longer, and more complicated labour compared with women selecting other less invasive analgesic modalities. Furthermore, in murine models, acute infection produces pain by directly activating sensory neurones that modulate inflammation.…”

Expression and function of NOD-like receptors by human term gestation-associated tissues

“…Previous studies have produced an IL-1β response in the first trimester trophoblast cell line Sw.71 [12,13] and term cytotrophoblasts [14] using uric acid crystals, although no priming signal was used in these studies. Caspase-1 dependent IL-1β production in response to nigericin was also observed by the choriodecidua and amnion, corresponding to IL-1β production by fetal membrane explants in response to ATP treatment [15,38].…”