VIP modulates the pro-inflammatory maternal response inducing tolerance to trophoblast-cells

FRACCAROLI; LAROCCA L; CALAFAT M; ROCA V; PEREZ LEIROS C; RAMHORST R

Buenos Aires

Congreso; III Iberoamerican Congress of Neuroimmunomodulation (NIM); 2009

Seccion Argentina de la ISNIM

Successful embryo implantation occurs followed by a local pro-inflammatory and Th1 response, subsequently controlled by a Th2 response. VIP (vasoactive intestinal peptide) has anti-inflammatory effects and promotes tolerogenic/Th2 responses; then we investigated the regulatory role of VIP on human trophoblast cells, maternal pro-inflammatory response and trophoblast-maternal leukocyte interaction. First, we tested VIP effects directly on immortalized trophoblast cells (Swan 71) and after co culture with maternal fertile PBMCs as representative models of feto-maternal dialogue. Swan 71 cells express VPAC1 receptor and VIP induced their proliferation and the expression of leukaemia inhibitor factor (LIF), a proimplantatory marker. After the interaction with trophoblast cells, VIP significantly increased Foxp3, the frequency of  expression (pbCD4+CD25+Foxp3+ within maternal PBMCs and TGF<0.05 Mann Whitney test). In accordance, during the trophoblast-maternal PBMCs dialogue, VIP reduced IL-6, MCP-1, nitric oxide while increased IL-10 (p<0.05 Student t-test for each mediator). Moreover, trophoblast cells produced VIP which dose-dependently suppressed allomaternal response associated with a reduction of T-bet expression. Conclusion: VIP induced pro-implantatory markers and trophoblast cell proliferation while it controlled the initial pro-inflammatory response increasing maternal Tregs and anti-inflammatory cytokines in favor of fetal survival.