Barrientos, G.; Toro, A.; Moschansky, P.; Cohen, M.; Garcia, M.G.; Rose, M.; Maskin, B.; Sánchez-Margalet, V.; Blois, S.M.; Varone, C.L. "Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways" (2015) Placenta. 36(4):419-426
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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. © 2015 Elsevier Ltd. All rights reserved.


Documento: Artículo
Título:Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways
Autor:Barrientos, G.; Toro, A.; Moschansky, P.; Cohen, M.; Garcia, M.G.; Rose, M.; Maskin, B.; Sánchez-Margalet, V.; Blois, S.M.; Varone, C.L.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, IQUIBICEN CONICET, Buenos Aires, Argentina
Charité Center 12 Internal Medicine and Dermatology, Reproductive Medicine Research Group, Medicine University, Berlin, Germany
Laboratoire d'Hormonologie, Department of Gynaecology and Obstetrics, Geneva, Switzerland
Gene Therapy Laboratory, Facultad de Ciencias Biomédicas, Universidad Austral, Derqui-Buenos Aires, Argentina
Hospital Nacional Profesor Alejandro Posadas, Buenos Aires, Argentina
Departamento de Bioquímica Médica y Biología Molecular, Hospital Universitario Virgen Macarena, Universidad de Sevilla, Sevilla, Spain
Palabras clave:HLA-G; Leptin; Placenta; Signal transduction; 2 (2 amino 3 methoxyphenyl)chromone; 2 morpholino 8 phenylchromone; HLA G antigen; leptin; mitogen activated protein kinase kinase; phosphatidylinositol 3 kinase; protein kinase B; recombinant leptin; antisense oligodeoxynucleotide; HLA G antigen; leptin; phosphatidylinositol 3 kinase; protein kinase inhibitor; recombinant protein; antigen expression; Article; choriocarcinoma cell line; controlled study; embryo; explant; female; first trimester pregnancy; gene expression; hormone action; human; human cell; immune evasion; immune response; immunofluorescence; immunomodulation; in vitro study; placenta; priority journal; protein expression; reverse transcription polymerase chain reaction; signal transduction; syncytiotrophoblast; trophoblast; upregulation; Western blotting; adult; antagonists and inhibitors; cell line; chemistry; cytology; drug effects; gene expression regulation; gene silencing; genetics; immunology; metabolism; pregnancy; reproduction; third trimester pregnancy; tissue culture technique; trophoblast; Adult; Cell Line; Female; Gene Expression Regulation, Developmental; Gene Silencing; HLA-G Antigens; Humans; Leptin; MAP Kinase Signaling System; Oligodeoxyribonucleotides, Antisense; Phosphatidylinositol 3-Kinase; Placentation; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Third; Protein Kinase Inhibitors; Recombinant Proteins; Signal Transduction; Tissue Culture Techniques; Trophoblasts
Página de inicio:419
Página de fin:426
Título revista:Placenta
Título revista abreviado:Placenta
CAS:2 (2 amino 3 methoxyphenyl)chromone, 167869-21-8; 2 morpholino 8 phenylchromone, 154447-36-6; mitogen activated protein kinase kinase, 142805-58-1; phosphatidylinositol 3 kinase, 115926-52-8; protein kinase B, 148640-14-6; HLA-G Antigens; Leptin; Oligodeoxyribonucleotides, Antisense; Phosphatidylinositol 3-Kinase; Protein Kinase Inhibitors; Recombinant Proteins


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---------- APA ----------
Barrientos, G., Toro, A., Moschansky, P., Cohen, M., Garcia, M.G., Rose, M., Maskin, B.,..., Varone, C.L. (2015) . Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways. Placenta, 36(4), 419-426.
---------- CHICAGO ----------
Barrientos, G., Toro, A., Moschansky, P., Cohen, M., Garcia, M.G., Rose, M., et al. "Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways" . Placenta 36, no. 4 (2015) : 419-426.
---------- MLA ----------
Barrientos, G., Toro, A., Moschansky, P., Cohen, M., Garcia, M.G., Rose, M., et al. "Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways" . Placenta, vol. 36, no. 4, 2015, pp. 419-426.
---------- VANCOUVER ----------
Barrientos, G., Toro, A., Moschansky, P., Cohen, M., Garcia, M.G., Rose, M., et al. Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways. Placenta. 2015;36(4):419-426.