ROLE OF VIP IN TROPHOBLAST INVASION, VASCULAR REMODELING AND IMMUNOMODULATION DURING EARLY PREGNANCY

SARAH FINN-SELL; VANESA HAUK; CLAUDIA PEREZ LEIROS; RUHUL CHOUDHURY; DAIANA VOTA; JOHN APLIN; DANIEL PAPARINI; MAGDA KAROLCZACK-BAYATTI; ROSANNA RAMHORST

Manchester

Congreso; IFPA Congress; 2017

Deep placentation disorders are associated with impaired invasiveness of extravillous trophoblast cells (EVT) and vascular remodelling in a pro-inflammatory microenvironment. The vasoactive intestinal peptide (VIP) has anti-inflammatory, pro-secretory and vasodilating effects. However its role in pregnancy is still unclear. Objectives: Here we studied the expression and effects of VIP in human first trimester placenta and its modulation on decidual macrophages (dMA) and NK cells (dNK). Methods: Explants from placentas (5-10 weeks) were treated with VIP ±VIP-neutralizing antibody (α-VIP) and outgrowth was measured. VIP expression and spiral artery (spA) remodelling were studied by immunostaining assays. Positive selection with CD14 or CD56 immunomagnetic beads was used to isolate dMA and dNK. Both cells were treated with VIP. Gene expression and protein secretion was studied by qRT-PCR and BioPlex assay, respectively.Results: Explants treated with VIP increased the outgrowth of EVT (592±68.6 A.U.) and the effect was prevented by α-VIP (266±100.1 A.U.). VIP was expressed in the cell columns, the villous and EVT cells. Moreover, HLA-G/VIP positive cells were found in both the walls and lumens of spA being remodelled. The BioPlex assay showed high levels of IL-1β and IL-6 and low concentration of pro-inflammatory cytokines (TNF-α, IL-12). When the explants were treated with VIP, the anti-inflammatory cytokine IL-10 and chemokines IL-8, RANTES, IP-10 and MCP-1 were increased with no changes in pro-inflammatory cytokines. VIP increased IL-10 and reduced IL-2 and IL-12 in dMA whereas it reduced IL-1β and IL-8 in dNK. VIP also increased metalloprotease-2 in dMA but not in dNK.Conclusion: The results suggest that VIP is produced by trophoblast cells and support its role in migration, invasion and spA remodelling by EVT. Moreover, VIP regulates the immune microenvironment through inducing chemokine expression and increasing IL-10 production without changing pro-inflammatory cytokines.