Hypoxia and oxidative stress induce sterile placental inflammation in vitro

Abstract Fetal growth restriction (FGR) and stillbirth are associated with placental dysfunction and inflammation and hypoxia, oxidative and nitrative stress are implicated in placental damage. Damage-associated molecular patterns (DAMPs) are elevated in pregnancies at increased risk of FGR and stil...

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Autores principales:	Bernadette C. Baker, Alexander E. P. Heazell, Colin Sibley, Rachael Wright, Helen Bischof, Frances Beards, Tatiana Guevara, Sylvie Girard, Rebecca L. Jones
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0082fca370eb455db03a738d71c33065
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spelling	oai:doaj.org-article:0082fca370eb455db03a738d71c330652021-12-02T18:17:40ZHypoxia and oxidative stress induce sterile placental inflammation in vitro10.1038/s41598-021-86268-12045-2322https://doaj.org/article/0082fca370eb455db03a738d71c330652021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86268-1https://doaj.org/toc/2045-2322Abstract Fetal growth restriction (FGR) and stillbirth are associated with placental dysfunction and inflammation and hypoxia, oxidative and nitrative stress are implicated in placental damage. Damage-associated molecular patterns (DAMPs) are elevated in pregnancies at increased risk of FGR and stillbirth and are associated with increase in pro-inflammatory placental cytokines. We hypothesised that placental insults lead to release of DAMPs, promoting placental inflammation. Placental tissue from uncomplicated pregnancies was exposed in vitro to hypoxia, oxidative or nitrative stress. Tissue production and release of DAMPs and cytokines was determined. Oxidative stress and hypoxia caused differential release of DAMPs including uric acid, HMGB1, S100A8, cell-free fetal DNA, S100A12 and HSP70. After oxidative stress pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, TNFα, CCL2) were increased both within explants and in conditioned culture medium. Hypoxia increased tissue IL-1α/β, IL-6, IL-8 and TNFα levels, and release of IL-1α, IL-6 and IL-8, whereas CCL2 and IL-10 were reduced. IL1 receptor antagonist (IL1Ra) treatment prevented hypoxia- and oxidative stress-induced IL-6 and IL-8 release. These findings provide evidence that relevant stressors induce a sterile inflammatory profile in placental tissue which can be partially blocked by IL1Ra suggesting this agent has translational potential to prevent placental inflammation evident in FGR and stillbirth.Bernadette C. BakerAlexander E. P. HeazellColin SibleyRachael WrightHelen BischofFrances BeardsTatiana GuevaraSylvie GirardRebecca L. JonesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bernadette C. Baker Alexander E. P. Heazell Colin Sibley Rachael Wright Helen Bischof Frances Beards Tatiana Guevara Sylvie Girard Rebecca L. Jones Hypoxia and oxidative stress induce sterile placental inflammation in vitro
description	Abstract Fetal growth restriction (FGR) and stillbirth are associated with placental dysfunction and inflammation and hypoxia, oxidative and nitrative stress are implicated in placental damage. Damage-associated molecular patterns (DAMPs) are elevated in pregnancies at increased risk of FGR and stillbirth and are associated with increase in pro-inflammatory placental cytokines. We hypothesised that placental insults lead to release of DAMPs, promoting placental inflammation. Placental tissue from uncomplicated pregnancies was exposed in vitro to hypoxia, oxidative or nitrative stress. Tissue production and release of DAMPs and cytokines was determined. Oxidative stress and hypoxia caused differential release of DAMPs including uric acid, HMGB1, S100A8, cell-free fetal DNA, S100A12 and HSP70. After oxidative stress pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, TNFα, CCL2) were increased both within explants and in conditioned culture medium. Hypoxia increased tissue IL-1α/β, IL-6, IL-8 and TNFα levels, and release of IL-1α, IL-6 and IL-8, whereas CCL2 and IL-10 were reduced. IL1 receptor antagonist (IL1Ra) treatment prevented hypoxia- and oxidative stress-induced IL-6 and IL-8 release. These findings provide evidence that relevant stressors induce a sterile inflammatory profile in placental tissue which can be partially blocked by IL1Ra suggesting this agent has translational potential to prevent placental inflammation evident in FGR and stillbirth.
format	article
author	Bernadette C. Baker Alexander E. P. Heazell Colin Sibley Rachael Wright Helen Bischof Frances Beards Tatiana Guevara Sylvie Girard Rebecca L. Jones
author_facet	Bernadette C. Baker Alexander E. P. Heazell Colin Sibley Rachael Wright Helen Bischof Frances Beards Tatiana Guevara Sylvie Girard Rebecca L. Jones
author_sort	Bernadette C. Baker
title	Hypoxia and oxidative stress induce sterile placental inflammation in vitro
title_short	Hypoxia and oxidative stress induce sterile placental inflammation in vitro
title_full	Hypoxia and oxidative stress induce sterile placental inflammation in vitro
title_fullStr	Hypoxia and oxidative stress induce sterile placental inflammation in vitro
title_full_unstemmed	Hypoxia and oxidative stress induce sterile placental inflammation in vitro
title_sort	hypoxia and oxidative stress induce sterile placental inflammation in vitro
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0082fca370eb455db03a738d71c33065
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Hypoxia and oxidative stress induce sterile placental inflammation in vitro

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