INVESTIGADORES
BARRIENTOS Gabriela Laura
artículos
Título:
Leptin promotes HLA-G expression on placental trophoblasts via the MEK/Erk and PI3K signaling pathways
Autor/es:
BARRIENTOS, G; TORO, A; MOSCHANSKY, P; COHEN, M; GARCIA, MG; ROSE, M; MASKIN, B; SÁNCHEZ-MARGALET, V; BLOIS, SM; VARONE, CL
Revista:
PLACENTA
Editorial:
W B SAUNDERS CO LTD
Referencias:
Lugar: Londres; Año: 2015 vol. 36 p. 419 - 426
ISSN:
0143-4004
Resumen:
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.