Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal Membranes
Context:Sterile inflammation has been shown to play a key role in the rupture of the fetal membranes (FMs). Moreover, an early and exacerbated runaway inflammation can evolve into a preterm premature rupture of membranes and lead to potential preterm birth. In this context, we investigated the recep...
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doaj-ff2d10876f38427cafcbf908ada6fbd72020-11-25T02:29:33ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-06-011110.3389/fphys.2020.00581540367Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal MembranesHéléna Choltus0Marilyne Lavergne1Corinne Belville2Denis Gallot3Denis Gallot4Régine Minet-Quinard5Régine Minet-Quinard6Julie Durif7Loïc Blanchon8Vincent Sapin9Vincent Sapin10CNRS, INSERM, GReD, Université Clermont Auvergne, Clermont-Ferrand, FranceCNRS, INSERM, GReD, Université Clermont Auvergne, Clermont-Ferrand, FranceCNRS, INSERM, GReD, Université Clermont Auvergne, Clermont-Ferrand, FranceCNRS, INSERM, GReD, Université Clermont Auvergne, Clermont-Ferrand, FranceCHU de Clermont-Ferrand, Obstetrics and Gynecology Department, Clermont-Ferrand, FranceCNRS, INSERM, GReD, Université Clermont Auvergne, Clermont-Ferrand, FranceCHU de Clermont-Ferrand, Biochemistry and Molecular Genetic Department, Clermont-Ferrand, FranceCHU de Clermont-Ferrand, Biochemistry and Molecular Genetic Department, Clermont-Ferrand, FranceCNRS, INSERM, GReD, Université Clermont Auvergne, Clermont-Ferrand, FranceCNRS, INSERM, GReD, Université Clermont Auvergne, Clermont-Ferrand, FranceCHU de Clermont-Ferrand, Biochemistry and Molecular Genetic Department, Clermont-Ferrand, FranceContext:Sterile inflammation has been shown to play a key role in the rupture of the fetal membranes (FMs). Moreover, an early and exacerbated runaway inflammation can evolve into a preterm premature rupture of membranes and lead to potential preterm birth. In this context, we investigated the receptor for advanced glycation end products (RAGE), an axis implied in physiological sterile inflammation, in conjunction with two major ligands: AGEs and High-Mobility Group Box 1 (HMGB1). Our first objective was to determine the spatiotemporal expression profiles of the different actors of the RAGE-signaling axis in human FMs, including its intracellular adaptors Diaphanous-1 and Myd88. Our second goal was to evaluate the functionality of RAGE signaling in terms of FMs inflammation.MethodsThe presence of the actors (RAGE, HMGB1, Myd88, and Diaphanous-1) at the mRNA level was investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in the human amnion and choriodecidua at the three trimesters and at term. Measurements were conducted at two distinct zones: the zone of intact morphology (ZIM) and the zone of altered morphology (ZAM). Then, proteins were quantified using Western blot analysis, and their localization was evaluated by immunofluorescence in term tissues. In addition, pro-inflammatory cytokine secretion was quantified using a Multiplex assay after the treatment of amnion and choriodecidua explants with two RAGE ligands (AGEs and HMGB1) in the absence or presence of a RAGE inhibitor (SAGEs).ResultsThe FMs expressed the RAGE-signaling actors throughout pregnancy. At term, RNA and protein overexpression of the RAGE, HMGB1, and Diaphanous-1 were found in the amnion when compared to the choriodecidua, and the RAGE was overexpressed in the ZAM when compared to the ZIM. The two RAGE ligands (AGEs and HMGB1) induced differential cytokine production (IL1β and TNFα) in the amnion and choriodecidua.ConclusionConsidered together, these results indicate that RAGE signaling is present and functional in human FMs. Our work opens the way to a better understanding of FMs weakening dependent on a RAGE-based sterile inflammation.https://www.frontiersin.org/article/10.3389/fphys.2020.00581/fullfetal membranesRAGEalarminssterile inflammationrupture of fetal membranes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Héléna Choltus Marilyne Lavergne Corinne Belville Denis Gallot Denis Gallot Régine Minet-Quinard Régine Minet-Quinard Julie Durif Loïc Blanchon Vincent Sapin Vincent Sapin |
spellingShingle |
Héléna Choltus Marilyne Lavergne Corinne Belville Denis Gallot Denis Gallot Régine Minet-Quinard Régine Minet-Quinard Julie Durif Loïc Blanchon Vincent Sapin Vincent Sapin Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal Membranes Frontiers in Physiology fetal membranes RAGE alarmins sterile inflammation rupture of fetal membranes |
author_facet |
Héléna Choltus Marilyne Lavergne Corinne Belville Denis Gallot Denis Gallot Régine Minet-Quinard Régine Minet-Quinard Julie Durif Loïc Blanchon Vincent Sapin Vincent Sapin |
author_sort |
Héléna Choltus |
title |
Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal Membranes |
title_short |
Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal Membranes |
title_full |
Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal Membranes |
title_fullStr |
Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal Membranes |
title_full_unstemmed |
Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal Membranes |
title_sort |
occurrence of a rage-mediated inflammatory response in human fetal membranes |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2020-06-01 |
description |
Context:Sterile inflammation has been shown to play a key role in the rupture of the fetal membranes (FMs). Moreover, an early and exacerbated runaway inflammation can evolve into a preterm premature rupture of membranes and lead to potential preterm birth. In this context, we investigated the receptor for advanced glycation end products (RAGE), an axis implied in physiological sterile inflammation, in conjunction with two major ligands: AGEs and High-Mobility Group Box 1 (HMGB1). Our first objective was to determine the spatiotemporal expression profiles of the different actors of the RAGE-signaling axis in human FMs, including its intracellular adaptors Diaphanous-1 and Myd88. Our second goal was to evaluate the functionality of RAGE signaling in terms of FMs inflammation.MethodsThe presence of the actors (RAGE, HMGB1, Myd88, and Diaphanous-1) at the mRNA level was investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in the human amnion and choriodecidua at the three trimesters and at term. Measurements were conducted at two distinct zones: the zone of intact morphology (ZIM) and the zone of altered morphology (ZAM). Then, proteins were quantified using Western blot analysis, and their localization was evaluated by immunofluorescence in term tissues. In addition, pro-inflammatory cytokine secretion was quantified using a Multiplex assay after the treatment of amnion and choriodecidua explants with two RAGE ligands (AGEs and HMGB1) in the absence or presence of a RAGE inhibitor (SAGEs).ResultsThe FMs expressed the RAGE-signaling actors throughout pregnancy. At term, RNA and protein overexpression of the RAGE, HMGB1, and Diaphanous-1 were found in the amnion when compared to the choriodecidua, and the RAGE was overexpressed in the ZAM when compared to the ZIM. The two RAGE ligands (AGEs and HMGB1) induced differential cytokine production (IL1β and TNFα) in the amnion and choriodecidua.ConclusionConsidered together, these results indicate that RAGE signaling is present and functional in human FMs. Our work opens the way to a better understanding of FMs weakening dependent on a RAGE-based sterile inflammation. |
topic |
fetal membranes RAGE alarmins sterile inflammation rupture of fetal membranes |
url |
https://www.frontiersin.org/article/10.3389/fphys.2020.00581/full |
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