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

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....

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Detalles Bibliográficos
Autores principales: Fraccaroli, L., Alfieri, J., Larocca, L., Calafat, M., Roca, V., Lombardi, E., Ramhorst, R., Leirós, C.P.
Formato: JOUR
Materias:
Early pregnancy
Human implantation
Tolerance and pregnancy
VIP
interleukin 10
interleukin 6
leukemia inhibitory factor
monocyte chemotactic protein 1
nitric oxide
nitrite
transcription factor FOXP3
transcription factor T bet
transforming growth factor beta
vasoactive intestinal polypeptide
vasoactive intestinal polypeptide antagonist
vasoactive intestinal polypeptide receptor
autacoid
antiinflammatory activity
article
CD4+ CD25+ T lymphocyte
cell line
cell proliferation
coculture
controlled study
dose response
flow cytometry
human
human cell
immunological tolerance
immunomodulation
inflammation
nidation
peripheral blood mononuclear cell
priority journal
protein expression
reverse transcription polymerase chain reaction
statistical analysis
Swan 71 cell
trophoblast
Western blotting
drug antagonism
drug effect
female
immunology
metabolism
mononuclear cell
pregnancy
Cell Line
Cell Proliferation
Coculture Techniques
Dose-Response Relationship, Drug
Embryo Implantation
Female
Humans
Immune Tolerance
Inflammation Mediators
Interleukin-10
Leukocytes, Mononuclear
Pregnancy
Receptors, Vasoactive Intestinal Peptide
Trophoblasts
Vasoactive Intestinal Peptide
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00071188_v156_n1_p116_Fraccaroli
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario: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 β 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. © 2008 The British Pharmacological Society.

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