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- Title
VIP modulates the pro-inflammatory maternal response, inducing tolerance to trophoblast cells.
- Authors
Fraccaroli, Laura; Alfieri, Julio; Larocca, Luciana; Calafat, Mario; Roca, Valeria; Lombardi, Eduardo; Ramhorst, Rosanna; Leirós, Claudia Pérez; Leirós, Claudia Pérez
- Abstract
<bold>Background and Purpose: </bold>Successful embryo implantation is followed by a local pro-inflammatory and Th1 response, subsequently controlled by a Th2 response. Vasoactive intestinal peptide (VIP) has anti-inflammatory effects and promotes tolerogenic/Th2 responses while favouring embryonic development. We investigated the potential regulatory role of VIP on human trophoblast cells, maternal pro-inflammatory responses and trophoblast-maternal leukocyte interactions.<bold>Experimental Approach: </bold>We tested VIP effects directly on a trophoblast cell line (Swan 71 cells) and after co-culture with maternal peripheral blood mononuclear cells (PBMCs) as models of the feto-maternal dialogue. We also co-cultured maternal and paternal PBMCs to test effects of endogenous VIP on maternal alloresponses.<bold>Key Results: </bold>Swan 71 cells express VPAC(1) receptors and VIP induced their proliferation and the expression of leukaemia inhibitor factor, a pro-implantatory marker. After interaction with trophoblast cells, VIP increased Foxp3, the proportion of CD4+CD25+Foxp3+ cells within maternal PBMCs and transforming growth factor beta expression. Also, during the trophoblast-maternal PBMCs interaction, VIP reduced pro-inflammatory mediators [interleukin (IL)-6, monocyte chemoattractant protein 1, nitric oxide], while increasing IL-10. Trophoblast cells produced VIP which dose-dependently suppressed allomaternal responses, accompanied by reduced expression of the T cell transcription factor, T-bet.<bold>Conclusions and Implications: </bold>Vasoactive intestinal peptide induced pro-implantatory markers and trophoblast cell proliferation, while controlling the initial pro-inflammatory response, by increasing maternal regulatory T cells and anti-inflammatory cytokines. As an autocrine regulatory peptide VIP might contribute to fetal survival through two mechanisms; a direct trophic effect on trophoblast cells and an immunomodulatory effect that favours tolerance to fetal antigens.
- Subjects
EMBRYOS; TROPHOBLAST; CYTOKINES; T cells; INFLAMMATORY mediators
- Publication
British Journal of Pharmacology, 2009, Vol 156, Issue 1, p116
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1111/j.1476-5381.2008.00055.x