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Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation

Maternal obesity is associated with a wide spectrum of labour disorders, including preterm birth. Leptin, a pro-inflammatory adipokine and a key factor of obesity, is suspected to play a major role in these disorders. OB-R, its receptor, is expressed on macrophages and myocytes, two cell types criti...

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Autores principales: Wendremaire, Maeva, Lopez, Tatiana E., Barrichon, Marina, Zhang, Hang, Hadi, Tarik, Ye, Xiang-Yang, Neiers, Fabrice, Bardou, Marc, Sagot, Paul, Garrido, Carmen, Lirussi, Frédéric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946078/
https://www.ncbi.nlm.nih.gov/pubmed/35326405
http://dx.doi.org/10.3390/cells11060954
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author Wendremaire, Maeva
Lopez, Tatiana E.
Barrichon, Marina
Zhang, Hang
Hadi, Tarik
Ye, Xiang-Yang
Neiers, Fabrice
Bardou, Marc
Sagot, Paul
Garrido, Carmen
Lirussi, Frédéric
author_facet Wendremaire, Maeva
Lopez, Tatiana E.
Barrichon, Marina
Zhang, Hang
Hadi, Tarik
Ye, Xiang-Yang
Neiers, Fabrice
Bardou, Marc
Sagot, Paul
Garrido, Carmen
Lirussi, Frédéric
author_sort Wendremaire, Maeva
collection PubMed
description Maternal obesity is associated with a wide spectrum of labour disorders, including preterm birth. Leptin, a pro-inflammatory adipokine and a key factor of obesity, is suspected to play a major role in these disorders. OB-R, its receptor, is expressed on macrophages and myocytes, two cell types critical for labour onset. Macrophages secrete reactive oxygen species/pro-inflammatory cytokines, responsible for myometrial differentiation while myocytes control uterine contractions. In this study, we assessed the effect of leptin on myometrial contraction and differentiation using our validated co-culture model of human primary macrophages and myocytes. We demonstrated that leptin had a different effect on myocytes and macrophages depending on the dose. A low leptin concentration induced a tocolytic effect by preventing myocytes’ contraction, differentiation, and macrophage-induced ROS production. Additionally, leptin led to an increase in HLA-G expression, suggesting that the tocolytic effect of leptin may be driven by HLA-G, a tolerogenic molecule. Finally, we observed that recombinant HLA-G also prevented LPS-induced ROS production by macrophages. Altogether, these data provide a putative molecular mechanism by which leptin may induce immune tolerance and therefore interfere with labour-associated mechanisms. Therefore, HLA-G represents a potential innovative therapeutic target in the pharmacological management of preterm labour.
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spelling pubmed-89460782022-03-25 Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation Wendremaire, Maeva Lopez, Tatiana E. Barrichon, Marina Zhang, Hang Hadi, Tarik Ye, Xiang-Yang Neiers, Fabrice Bardou, Marc Sagot, Paul Garrido, Carmen Lirussi, Frédéric Cells Article Maternal obesity is associated with a wide spectrum of labour disorders, including preterm birth. Leptin, a pro-inflammatory adipokine and a key factor of obesity, is suspected to play a major role in these disorders. OB-R, its receptor, is expressed on macrophages and myocytes, two cell types critical for labour onset. Macrophages secrete reactive oxygen species/pro-inflammatory cytokines, responsible for myometrial differentiation while myocytes control uterine contractions. In this study, we assessed the effect of leptin on myometrial contraction and differentiation using our validated co-culture model of human primary macrophages and myocytes. We demonstrated that leptin had a different effect on myocytes and macrophages depending on the dose. A low leptin concentration induced a tocolytic effect by preventing myocytes’ contraction, differentiation, and macrophage-induced ROS production. Additionally, leptin led to an increase in HLA-G expression, suggesting that the tocolytic effect of leptin may be driven by HLA-G, a tolerogenic molecule. Finally, we observed that recombinant HLA-G also prevented LPS-induced ROS production by macrophages. Altogether, these data provide a putative molecular mechanism by which leptin may induce immune tolerance and therefore interfere with labour-associated mechanisms. Therefore, HLA-G represents a potential innovative therapeutic target in the pharmacological management of preterm labour. MDPI 2022-03-10 /pmc/articles/PMC8946078/ /pubmed/35326405 http://dx.doi.org/10.3390/cells11060954 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wendremaire, Maeva
Lopez, Tatiana E.
Barrichon, Marina
Zhang, Hang
Hadi, Tarik
Ye, Xiang-Yang
Neiers, Fabrice
Bardou, Marc
Sagot, Paul
Garrido, Carmen
Lirussi, Frédéric
Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation
title Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation
title_full Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation
title_fullStr Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation
title_full_unstemmed Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation
title_short Leptin-Induced HLA-G Inhibits Myometrial Contraction and Differentiation
title_sort leptin-induced hla-g inhibits myometrial contraction and differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946078/
https://www.ncbi.nlm.nih.gov/pubmed/35326405
http://dx.doi.org/10.3390/cells11060954
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