Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways

Autores
Barrientos, Gabriela Laura; Toro, Ayelen Rayen; Monschanski, P; Cohen, M.; García, Mariana Gabriela; Rose, M.; Maskin, Bernardo; Sanchez Margalet, V.; Blois, Sandra M.; Varone, Cecilia Laura
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Introduction: The development of the human haemochorial placenta requires complex regulatory mechanisms to protect invasive trophoblast cells from cytotoxic responses elicited by maternal immune cells. Leptin, the adipocyte derived hormone encoded by the Lep gene, is synthesized by placental trophoblasts and exerts pleiotropic effects on the immune system, including the promotion of inflammation and the activation of T cell responses. Methods: To address its possible involvement in the modulation of maternal immune responses during pregnancy, we investigated the effect of leptin on the expression of the class Ib histocompatibility antigen HLA-G as one of the chief immunosuppressive strategies used by trophoblast cells. Results: In vitro incubation of the trophoblast derived Swan 71 and JEG-3 cell lines with 25-50 ng/ml recombinant leptin significantly boosted HLA-G mRNA and protein expression, and this effect was abrogated upon pharmacological inhibition of the PI3K-Akt and MEK-Erk signaling pathways. A similar stimulatory effect of leptin was observed in term placental tissue explants, though 10-fold higher doses were required for stimulation. Further, JEG-3 cells treated with a leptin antisense oligodeoxynucleotide displayed decreased HLA-G expression levels, which were partially recovered by addition of stimulating doses of exogenous hormone. Immunofluorescence and qPCR analysis confirmed leptin biosynthesis in placental tissue, further showing that invasive extravillous trophoblast cells were a main source of this hormone during the first trimester of normal pregnancies. Discussion: Taken together, our results show that leptin acts as an autocrine/paracrine signal promoting HLA-G expression in placental trophoblasts suggesting an important role in the regulation of immune evasion mechanisms at the fetal maternal interface.
Fil: Barrientos, Gabriela Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Toro, Ayelen Rayen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Monschanski, P. Medicine University Berlin; Alemania
Fil: Cohen, M.. Universidad de Ginebra; Suiza
Fil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina
Fil: Rose, M.. Medicine University Berlin; Alemania
Fil: Maskin, Bernardo. Hospital Nacional Profesor A. Posadas; Argentina
Fil: Sanchez Margalet, V.. Universidad de Sevilla; España
Fil: Blois, Sandra M.. Medicine University Berlin; Alemania
Fil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Materia
Hla-G
Leptin
Placenta
Signal Transduction
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/46904
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/46904
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathwaysBarrientos, Gabriela LauraToro, Ayelen RayenMonschanski, PCohen, M.García, Mariana GabrielaRose, M.Maskin, BernardoSanchez Margalet, V.Blois, Sandra M.Varone, Cecilia LauraHla-GLeptinPlacentaSignal Transductionhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Introduction: The development of the human haemochorial placenta requires complex regulatory mechanisms to protect invasive trophoblast cells from cytotoxic responses elicited by maternal immune cells. Leptin, the adipocyte derived hormone encoded by the Lep gene, is synthesized by placental trophoblasts and exerts pleiotropic effects on the immune system, including the promotion of inflammation and the activation of T cell responses. Methods: To address its possible involvement in the modulation of maternal immune responses during pregnancy, we investigated the effect of leptin on the expression of the class Ib histocompatibility antigen HLA-G as one of the chief immunosuppressive strategies used by trophoblast cells. Results: In vitro incubation of the trophoblast derived Swan 71 and JEG-3 cell lines with 25-50 ng/ml recombinant leptin significantly boosted HLA-G mRNA and protein expression, and this effect was abrogated upon pharmacological inhibition of the PI3K-Akt and MEK-Erk signaling pathways. A similar stimulatory effect of leptin was observed in term placental tissue explants, though 10-fold higher doses were required for stimulation. Further, JEG-3 cells treated with a leptin antisense oligodeoxynucleotide displayed decreased HLA-G expression levels, which were partially recovered by addition of stimulating doses of exogenous hormone. Immunofluorescence and qPCR analysis confirmed leptin biosynthesis in placental tissue, further showing that invasive extravillous trophoblast cells were a main source of this hormone during the first trimester of normal pregnancies. Discussion: Taken together, our results show that leptin acts as an autocrine/paracrine signal promoting HLA-G expression in placental trophoblasts suggesting an important role in the regulation of immune evasion mechanisms at the fetal maternal interface.Fil: Barrientos, Gabriela Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Toro, Ayelen Rayen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Monschanski, P. Medicine University Berlin; AlemaniaFil: Cohen, M.. Universidad de Ginebra; SuizaFil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; ArgentinaFil: Rose, M.. Medicine University Berlin; AlemaniaFil: Maskin, Bernardo. Hospital Nacional Profesor A. Posadas; ArgentinaFil: Sanchez Margalet, V.. Universidad de Sevilla; EspañaFil: Blois, Sandra M.. Medicine University Berlin; AlemaniaFil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaW B Saunders Co Ltd2015-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/46904Barrientos, Gabriela Laura; Toro, Ayelen Rayen; Monschanski, P; Cohen, M.; García, Mariana Gabriela; et al.; Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways; W B Saunders Co Ltd; Placenta; 36; 4; 4-2015; 419-4260143-4004CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.placentajournal.org/article/S0143-4004%2815%2900036-3/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.placenta.2015.01.006info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0143400415000363info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:40:40Zoai:ri.conicet.gov.ar:11336/46904instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-17 10:40:40.729CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways
title Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways
spellingShingle Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways
Barrientos, Gabriela Laura
Hla-G
Leptin
Placenta
Signal Transduction
title_short Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways
title_full Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways
title_fullStr Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways
title_full_unstemmed Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways
title_sort Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways
dc.creator.none.fl_str_mv Barrientos, Gabriela Laura
Toro, Ayelen Rayen
Monschanski, P
Cohen, M.
García, Mariana Gabriela
Rose, M.
Maskin, Bernardo
Sanchez Margalet, V.
Blois, Sandra M.
Varone, Cecilia Laura
author Barrientos, Gabriela Laura
author_facet Barrientos, Gabriela Laura
Toro, Ayelen Rayen
Monschanski, P
Cohen, M.
García, Mariana Gabriela
Rose, M.
Maskin, Bernardo
Sanchez Margalet, V.
Blois, Sandra M.
Varone, Cecilia Laura
author_role author
author2 Toro, Ayelen Rayen
Monschanski, P
Cohen, M.
García, Mariana Gabriela
Rose, M.
Maskin, Bernardo
Sanchez Margalet, V.
Blois, Sandra M.
Varone, Cecilia Laura
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hla-G
Leptin
Placenta
Signal Transduction
topic Hla-G
Leptin
Placenta
Signal Transduction
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Introduction: The development of the human haemochorial placenta requires complex regulatory mechanisms to protect invasive trophoblast cells from cytotoxic responses elicited by maternal immune cells. Leptin, the adipocyte derived hormone encoded by the Lep gene, is synthesized by placental trophoblasts and exerts pleiotropic effects on the immune system, including the promotion of inflammation and the activation of T cell responses. Methods: To address its possible involvement in the modulation of maternal immune responses during pregnancy, we investigated the effect of leptin on the expression of the class Ib histocompatibility antigen HLA-G as one of the chief immunosuppressive strategies used by trophoblast cells. Results: In vitro incubation of the trophoblast derived Swan 71 and JEG-3 cell lines with 25-50 ng/ml recombinant leptin significantly boosted HLA-G mRNA and protein expression, and this effect was abrogated upon pharmacological inhibition of the PI3K-Akt and MEK-Erk signaling pathways. A similar stimulatory effect of leptin was observed in term placental tissue explants, though 10-fold higher doses were required for stimulation. Further, JEG-3 cells treated with a leptin antisense oligodeoxynucleotide displayed decreased HLA-G expression levels, which were partially recovered by addition of stimulating doses of exogenous hormone. Immunofluorescence and qPCR analysis confirmed leptin biosynthesis in placental tissue, further showing that invasive extravillous trophoblast cells were a main source of this hormone during the first trimester of normal pregnancies. Discussion: Taken together, our results show that leptin acts as an autocrine/paracrine signal promoting HLA-G expression in placental trophoblasts suggesting an important role in the regulation of immune evasion mechanisms at the fetal maternal interface.
Fil: Barrientos, Gabriela Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Toro, Ayelen Rayen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Monschanski, P. Medicine University Berlin; Alemania
Fil: Cohen, M.. Universidad de Ginebra; Suiza
Fil: García, Mariana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ciencias Biomédicas. Laboratorio de Terapia Genética; Argentina
Fil: Rose, M.. Medicine University Berlin; Alemania
Fil: Maskin, Bernardo. Hospital Nacional Profesor A. Posadas; Argentina
Fil: Sanchez Margalet, V.. Universidad de Sevilla; España
Fil: Blois, Sandra M.. Medicine University Berlin; Alemania
Fil: Varone, Cecilia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
description Introduction: The development of the human haemochorial placenta requires complex regulatory mechanisms to protect invasive trophoblast cells from cytotoxic responses elicited by maternal immune cells. Leptin, the adipocyte derived hormone encoded by the Lep gene, is synthesized by placental trophoblasts and exerts pleiotropic effects on the immune system, including the promotion of inflammation and the activation of T cell responses. Methods: To address its possible involvement in the modulation of maternal immune responses during pregnancy, we investigated the effect of leptin on the expression of the class Ib histocompatibility antigen HLA-G as one of the chief immunosuppressive strategies used by trophoblast cells. Results: In vitro incubation of the trophoblast derived Swan 71 and JEG-3 cell lines with 25-50 ng/ml recombinant leptin significantly boosted HLA-G mRNA and protein expression, and this effect was abrogated upon pharmacological inhibition of the PI3K-Akt and MEK-Erk signaling pathways. A similar stimulatory effect of leptin was observed in term placental tissue explants, though 10-fold higher doses were required for stimulation. Further, JEG-3 cells treated with a leptin antisense oligodeoxynucleotide displayed decreased HLA-G expression levels, which were partially recovered by addition of stimulating doses of exogenous hormone. Immunofluorescence and qPCR analysis confirmed leptin biosynthesis in placental tissue, further showing that invasive extravillous trophoblast cells were a main source of this hormone during the first trimester of normal pregnancies. Discussion: Taken together, our results show that leptin acts as an autocrine/paracrine signal promoting HLA-G expression in placental trophoblasts suggesting an important role in the regulation of immune evasion mechanisms at the fetal maternal interface.
publishDate 2015
dc.date.none.fl_str_mv 2015-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/46904
Barrientos, Gabriela Laura; Toro, Ayelen Rayen; Monschanski, P; Cohen, M.; García, Mariana Gabriela; et al.; Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways; W B Saunders Co Ltd; Placenta; 36; 4; 4-2015; 419-426
0143-4004
CONICET Digital
CONICET
url http://hdl.handle.net/11336/46904
identifier_str_mv Barrientos, Gabriela Laura; Toro, Ayelen Rayen; Monschanski, P; Cohen, M.; García, Mariana Gabriela; et al.; Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways; W B Saunders Co Ltd; Placenta; 36; 4; 4-2015; 419-426
0143-4004
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.placentajournal.org/article/S0143-4004%2815%2900036-3/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.placenta.2015.01.006
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0143400415000363
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv W B Saunders Co Ltd
publisher.none.fl_str_mv W B Saunders Co Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.000565

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