Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways
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 trophobl...
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paper:paper_01434004_v36_n4_p419_Barrientos2023-06-08T15:11:50Z Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways Varone, Cecilia Laura 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 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. Fil:Varone, C.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01434004_v36_n4_p419_Barrientos http://hdl.handle.net/20.500.12110/paper_01434004_v36_n4_p419_Barrientos |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Varone, Cecilia Laura Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways |
| topic_facet |
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 |
| 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. © 2015 Elsevier Ltd. All rights reserved. |
| author |
Varone, Cecilia Laura |
| author_facet |
Varone, Cecilia Laura |
| author_sort |
Varone, Cecilia Laura |
| title |
Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways |
| 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 |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01434004_v36_n4_p419_Barrientos http://hdl.handle.net/20.500.12110/paper_01434004_v36_n4_p419_Barrientos |
| work_keys_str_mv |
AT varonececilialaura leptinpromoteshlagexpressiononplacentaltrophoblastsviathemekerkandpi3ksignalingpathways |
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1768542831554592768 |