Contribution of Vasoactive Intestinal Peptide to Immune Homeostasis in Trophoblast-Maternal Leukocyte Interaction under LPS Stimulation

FRACCAROLI L; GRASSO E; HAUK V; CORTELEZZI M; PÉREZ LEIRÓS C; RAMHORST R

NEUROIMMUNOMODULATION.

KARGER

Lugar: Basel; Año: 2014 vol. 21 p. 21 - 30

1021-7401

Background/Aims The maternal-fetal interface is a unique immunological site that generates an adequate microenvironment during pregnancy, recognizing and eliminating infections and tolerating the trophoblast/placenta unit. For that purpose, trophoblast cells display several tolerogenic mechanisms to allow fetal survival, as the production of the neuropeptide VIP (vasoactive intestinal peptide). Here we investigated the contribution of VIP to maintain the homeostasis at the maternal-placental interface under LPS stimula¬¬¬tion. Methods We performed co cultures between trophoblast cells (Swan-71 cell line) and maternal leukocytes obtained from fertile women as an in vitro model of maternal-placental interaction; and we focused on LPS effects on the modulation of VIP and their receptors (VPAC1 and VPAC2). Results VIP could prevent the up-regulation of IL-6, MCP-1 and nitrites production and mantain the production of IL-10 and TGFβ under LPS (10 µg ml-1) stimulation after 48 h of co cultures. To deepen into the mechanisms of how VIP could contribute to a tolerogenic microenvironment even in the presence of LPS, we investigated VIP production by maternal leukocytes and we observed a significant increase in the frequency of CD4+VIP+ cells after the interaction with Swan-71 cells in presence of LPS. LPS increased VIP and the inducible receptor VPAC2 expression directly on trophoblast cells in a dose and time dependent manner. Conclusions The present results suggest that VIP might act as an additional homestatic mechanism during early stages at the maternal-placental interface to control exacerbated inflammatory responses as the ones observed in intrauterine infections.