title: Vasoactive Intestinal Peptide modulates trophoblast-derived cell line function and interaction with phagocytic cells through autocrine pathways.
abstract: Trophoblast cells migrate and invade the decidual stroma in a tightly regulated process to maintain immune homeostasis at the maternal-placental interface during the first weeks of pregnancy. Locally synthesized factors modulate trophoblast cell function and their interaction with maternal leukocytes to promote the silent clearance of apoptotic cells. The vasoactive intestinal peptide (VIP) is a pleiotropic polypeptide with trophic and anti-inflammatory effects in murine pregnancy models. We explored the effect of VIP on two human first trimester trophoblast cell lines, particularly on their migration, invasiveness and interaction with phagocytic cells, and the signalling and regulatory pathways involved. We found that VIP enhanced trophoblast cell migration and invasion through the activation of high affinity VPAC receptors and PKA-CRE signalling pathways. VIP knocked-down trophoblast cells showed reduced migration in basal and leukemic inhibitor factor (LIF)-elicited conditions. In parallel, VIP-silenced trophoblast cells failed to induce the phagocytosis of apoptotic bodies and the expression of immunosuppressant markers by human monocytes. Our results suggest that VIP-mediated autocrine pathways regulate trophoblast cell function and contribute to immune homeostasis maintenance at placentation and may provide new clues for therapeutic intervention in pregnancies complicated by defective deep placentation.
authors.affiliation: Laboratory of Immunopharmacology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Ciudad Universitaria, Pab. 2, (1428) Buenos Aires, Argentina.
authors.forename: Daiana
authors.initials: D
authors.lastname: Vota
authors.affiliation: Laboratory of Immunopharmacology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Ciudad Universitaria, Pab. 2, (1428) Buenos Aires, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Paparini
authors.affiliation: Laboratory of Immunopharmacology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Ciudad Universitaria, Pab. 2, (1428) Buenos Aires, Argentina.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Hauk
authors.affiliation: Laboratory of Placental Molecular Physiology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Ciudad Universitaria, Pab. 2, (1428) Buenos Aires, Argentina.
authors.forename: Ayelén
authors.initials: A
authors.lastname: Toro
authors.affiliation: Laboratory of Immunopharmacology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Ciudad Universitaria, Pab. 2, (1428) Buenos Aires, Argentina.
authors.forename: Fatima
authors.initials: F
authors.lastname: Merech
authors.affiliation: Laboratory of Placental Molecular Physiology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Ciudad Universitaria, Pab. 2, (1428) Buenos Aires, Argentina.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Varone
authors.affiliation: Laboratory of Immunopharmacology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Ciudad Universitaria, Pab. 2, (1428) Buenos Aires, Argentina.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Ramhorst
authors.affiliation: Laboratory of Immunopharmacology, Department of Biological Chemistry, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Ciudad Universitaria, Pab. 2, (1428) Buenos Aires, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pérez Leirós
mesh_terms: D019898:Autocrine Communication; D002460:Cell Line; D002465:Cell Movement; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D010586:Phagocytes / Q000166:cytology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011494:Protein Kinases / Q000378:metabolism; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism; D015398:Signal Transduction; D014327:Trophoblasts / Q000166:cytology*; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*
chemical_list: D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D011494:Protein Kinases