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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doaj-0082fca370eb455db03a738d71c330652021-04-04T11:30:16ZengNature Publishing GroupScientific Reports2045-23222021-03-0111111410.1038/s41598-021-86268-1Hypoxia and oxidative stress induce sterile placental inflammation in vitroBernadette C. Baker0Alexander E. P. Heazell1Colin Sibley2Rachael Wright3Helen Bischof4Frances Beards5Tatiana Guevara6Sylvie Girard7Rebecca L. Jones8Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of ManchesterMaternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of ManchesterMaternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of ManchesterMaternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of ManchesterMaternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of ManchesterMaternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of ManchesterMaternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of ManchesterFetomaternal and Neonatal Pathologies Research Axis, Sainte-Justine Hospital Research CenterMaternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of ManchesterAbstract 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.https://doi.org/10.1038/s41598-021-86268-1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bernadette C. Baker Alexander E. P. Heazell Colin Sibley Rachael Wright Helen Bischof Frances Beards Tatiana Guevara Sylvie Girard Rebecca L. Jones |
spellingShingle |
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 Scientific Reports |
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 Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-03-01 |
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. |
url |
https://doi.org/10.1038/s41598-021-86268-1 |
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