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Production and regulation of interleukin-1 family cytokines at the materno-fetal interface

April Rees Orcid Logo, Louis M. Scott, Aled Bryant Orcid Logo, April Rees, Billy Down, Ruth Jones Orcid Logo, Cathy Thornton Orcid Logo

Cytokine, Volume: 99, Pages: 194 - 202

Swansea University Authors: April Rees Orcid Logo, Aled Bryant Orcid Logo, Ruth Jones Orcid Logo, Cathy Thornton Orcid Logo

Abstract

IL-1 family members regulate innate immune responses, are produced by gestation-associated tissues, and have a role in healthy and adverse pregnancy outcomes. To better understand their role at the materno-fetal interface we used a human tissue explant model to map lipopolysaccharide (LPS)-stimulate...

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Published in: Cytokine
ISSN: 10434666
Published: 2017
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa34588
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Abstract: IL-1 family members regulate innate immune responses, are produced by gestation-associated tissues, and have a role in healthy and adverse pregnancy outcomes. To better understand their role at the materno-fetal interface we used a human tissue explant model to map lipopolysaccharide (LPS)-stimulated production of IL-1α, IL-1β, IL-18, IL-33, IL-1Ra, IL-18BPa, ST2 and IL-1RAcP by placenta, choriodecidua and amnion. Caspase-dependent processing of IL-1α, IL-1β, IL-18, and IL-33 and the ability of IL-1α, IL-1β, IL-18, and IL-33 to regulate the production of IL-1RA, IL-18BPa, ST2 and IL-1RAcP was also determined. LPS acted as a potent inducer of IL-1 family member expression especially in the placenta and choriodecidua with the response by the amnion restricted to IL-1β. Caspases-1, 4 and 8 contributed to LPS-stimulated production of IL-1 and IL-18, whereas calpain was required for IL-1 production. Exogenous administration of IL-1α, IL-1β, IL-18, and IL-33 lead to differential expression of IL-1Ra, IL-18BPa, ST2 and IL-1RAcP across all tissues examined. Most notable were the counter-regulatory effect of LPS on IL-1 and IL-1Ra in the amnion and the broad responsiveness of the amnion to IL-1 family cytokines for increased production of immunomodulatory peptides and soluble receptors. The placenta and membranes vary not only in their output of various IL-1 family members but also in their counter-regulatory mechanisms through endogenous inhibitory peptides, processing enzymes and soluble decoy receptors. This interactive network of inflammatory mediators likely contributes to innate defence mechanisms at the materno-fetal interface to limit, in particular, the detrimental effects of microbial invasion.
Keywords: Cytokines, IL-1 family, Placenta, Preterm labour, Reproductive Immunology.
College: Faculty of Medicine, Health and Life Sciences
Start Page: 194
End Page: 202