Document Detail

VIP modulates the pro-inflammatory maternal response, inducing tolerance to trophoblast cells.
MedLine Citation:
PMID:  19133995     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND PURPOSE: 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.
EXPERIMENTAL APPROACH: 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.
KEY RESULTS: 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.
CONCLUSIONS AND IMPLICATIONS: 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.
Laura Fraccaroli; Julio Alfieri; Luciana Larocca; Mario Calafat; Valeria Roca; Eduardo Lombardi; Rosanna Ramhorst; Claudia Pérez Leirós
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  156     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-12     Completed Date:  2009-05-18     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  116-26     Citation Subset:  IM    
Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.
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MeSH Terms
Cell Line
Cell Proliferation / drug effects
Coculture Techniques
Dose-Response Relationship, Drug
Embryo Implantation / immunology
Immune Tolerance
Inflammation Mediators / antagonists & inhibitors,  immunology,  metabolism
Interleukin-10 / immunology,  metabolism
Leukocytes, Mononuclear / immunology*,  metabolism
Pregnancy / immunology*
Receptors, Vasoactive Intestinal Peptide / metabolism
Trophoblasts / immunology*,  metabolism
Vasoactive Intestinal Peptide / immunology*,  metabolism,  pharmacology
Reg. No./Substance:
0/Inflammation Mediators; 0/Receptors, Vasoactive Intestinal Peptide; 130068-27-8/Interleukin-10; 37221-79-7/Vasoactive Intestinal Peptide

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