Role of the Macrophage Migration Inhibitory Factor (MIF) in the survival of first trimester human placenta under induced stress conditions
Abstract Macrophage Migration Inhibitory Factor (MIF) is a multifunctional molecule highly secreted by human placenta mainly in the early phases of pregnancy. Studies in different cells show that MIF is a pro-survival factor by binding to its receptor CD74. By using the in vitro model of placental e...
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2018
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oai:doaj.org-article:9109eb45726a45ad9b3a7553bafc58c52021-12-02T11:40:26ZRole of the Macrophage Migration Inhibitory Factor (MIF) in the survival of first trimester human placenta under induced stress conditions10.1038/s41598-018-29797-62045-2322https://doaj.org/article/9109eb45726a45ad9b3a7553bafc58c52018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-29797-6https://doaj.org/toc/2045-2322Abstract Macrophage Migration Inhibitory Factor (MIF) is a multifunctional molecule highly secreted by human placenta mainly in the early phases of pregnancy. Studies in different cells show that MIF is a pro-survival factor by binding to its receptor CD74. By using the in vitro model of placental explants from first trimester pregnancy, we investigated the role of MIF in the survival of placental cells under induced stress conditions that promote apoptosis or mimic the hypoxia/re-oxygenation (H/R) injury that placenta could suffer in vivo. We demonstrated that recombinant MIF (rMIF) treatment was able to reduce caspase-3 activation when cultures were challenged with the apoptosis-inducer Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) while, in the cultures exposed to H/R, the treatment with rMIF did not show any effect. However, a significant increase in caspase-3 and caspase-8 activation was found when H/R-exposed cultures, were treated with anti-MIF or anti-CD74 antibody. We also observed that under H/R, a significant amount of endogenous MIF was released into the medium, which could account for the lack of effect of rMIF added to the cultures. Our results demonstrate for the first time that the MIF/CD74 axis contributes to maintain trophoblast homeostasis, by preventing abnormal apoptotic death.Francesca IettaEloisa Amália Vieira FerroEstela BevilacquaLinda BenincasaEmanuela MaioliLuana PaulesuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) |
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Medicine R Science Q Francesca Ietta Eloisa Amália Vieira Ferro Estela Bevilacqua Linda Benincasa Emanuela Maioli Luana Paulesu Role of the Macrophage Migration Inhibitory Factor (MIF) in the survival of first trimester human placenta under induced stress conditions |
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Abstract Macrophage Migration Inhibitory Factor (MIF) is a multifunctional molecule highly secreted by human placenta mainly in the early phases of pregnancy. Studies in different cells show that MIF is a pro-survival factor by binding to its receptor CD74. By using the in vitro model of placental explants from first trimester pregnancy, we investigated the role of MIF in the survival of placental cells under induced stress conditions that promote apoptosis or mimic the hypoxia/re-oxygenation (H/R) injury that placenta could suffer in vivo. We demonstrated that recombinant MIF (rMIF) treatment was able to reduce caspase-3 activation when cultures were challenged with the apoptosis-inducer Carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) while, in the cultures exposed to H/R, the treatment with rMIF did not show any effect. However, a significant increase in caspase-3 and caspase-8 activation was found when H/R-exposed cultures, were treated with anti-MIF or anti-CD74 antibody. We also observed that under H/R, a significant amount of endogenous MIF was released into the medium, which could account for the lack of effect of rMIF added to the cultures. Our results demonstrate for the first time that the MIF/CD74 axis contributes to maintain trophoblast homeostasis, by preventing abnormal apoptotic death. |
format |
article |
author |
Francesca Ietta Eloisa Amália Vieira Ferro Estela Bevilacqua Linda Benincasa Emanuela Maioli Luana Paulesu |
author_facet |
Francesca Ietta Eloisa Amália Vieira Ferro Estela Bevilacqua Linda Benincasa Emanuela Maioli Luana Paulesu |
author_sort |
Francesca Ietta |
title |
Role of the Macrophage Migration Inhibitory Factor (MIF) in the survival of first trimester human placenta under induced stress conditions |
title_short |
Role of the Macrophage Migration Inhibitory Factor (MIF) in the survival of first trimester human placenta under induced stress conditions |
title_full |
Role of the Macrophage Migration Inhibitory Factor (MIF) in the survival of first trimester human placenta under induced stress conditions |
title_fullStr |
Role of the Macrophage Migration Inhibitory Factor (MIF) in the survival of first trimester human placenta under induced stress conditions |
title_full_unstemmed |
Role of the Macrophage Migration Inhibitory Factor (MIF) in the survival of first trimester human placenta under induced stress conditions |
title_sort |
role of the macrophage migration inhibitory factor (mif) in the survival of first trimester human placenta under induced stress conditions |
publisher |
Nature Portfolio |
publishDate |
2018 |
url |
https://doaj.org/article/9109eb45726a45ad9b3a7553bafc58c5 |
work_keys_str_mv |
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1718395594942185472 |