Vasoactive Intestinal Peptide modulates trophoblast-derived cell line function and interaction with phagocytic cells through autocrine pathways

VOTA D, PAPARINI D, HAUK V, TORO A, MERECH F, VARONE C, RAMHORST R AND PÉREZ LEIRÓS C

Scientific Reports

NPG

Año: 2016 vol. 23 p. 26364 - 26376

Trophoblast cells migrate and invade the decidual stroma in a tightly regulated process to maintainimmune homeostasis at the maternal-placental interface during the first weeks of pregnancy. Locallysynthesized factors modulate trophoblast cell function and their interaction with maternal leukocytesto promote the silent clearance of apoptotic cells. The vasoactive intestinal peptide (VIP) is a pleiotropicpolypeptide with trophic and anti-inflammatory effects in murine pregnancy models. We exploredthe 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 pathwaysinvolved. We found that VIP enhanced trophoblast cell migration and invasion through the activationof high affinity VPAC receptors and PKA-CRE signalling pathways. VIP knocked-down trophoblast cellsshowed 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 expressionof immunosuppressant markers by human monocytes. Our results suggest that VIP-mediated autocrinepathways regulate trophoblast cell function and contribute to immune homeostasis maintenance atplacentation and may provide new clues for therapeutic intervention in pregnancies complicated bydefective deep placentation.