Acetylcholine contributes to control the physiological inflammatory response during the peri-implantation period

PAPARINI D; GORI S; GRASSO E; SCORBO W; GALO G; PÉREZ LEIRÓS C, ; RAMHORST R*, ; SALAMONE G*

ACTA PHYSIOLOGICA

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2015 vol. 214 p. 237 - 247

1748-1708

Background: Maternal antigen-presenting cells attracted to the pregnantuterus interact with trophoblast cells and modulate their functional profileto favour immunosuppressant responses. Non-neuronal cholinergic systemis expressed in human cytotrophoblast cells and in immune cells withhomeostatic regulatory functions.Aim: The aim of this work was to evaluate whether non-neuronal acetyl-choline conditions maternal monocyte and DC migration and activationprofiles.Methods: We used an in vitro model resembling maternal?placental inter-face represented by the co-culture of human trophoblast cells (Swan-71cell line) and monocytes or DC.Results: When cytotrophoblast cells were treated with neostigmine (Neo)to concentrate endogenous acetylcholine levels, monocyte migration wasincreased. In parallel, high levels of IL-10 and decreased levels of TNF-awere observed upon interaction of maternal monocytes with trophoblastcells. This effect was synergized by Neo and was prevented by atropine, amuscarinic acetylcholine receptor antagonist. Similarly, trophoblast cellsincreased the migration of DC independently of Neo treatment; however,enhanced IL-10 and MCP-1 synthesis in trophoblast?DC co-cultures withno changes in TNF-a and IL-6 was observed. In fact, there were nochanges in HLA-DR, CD86 or CD83 expression. Finally, trophoblast cellstreated with Neo increased the expression of two antigen-presenting cellsattracting chemokines, MCP-1, MIP-1a and RANTES through muscarinicreceptors, and it was prevented by atropine.Conclusions: Our present results support a novel role of acetylcholinesynthesized by trophoblast cells to modulate antigen-presenting cell migra-tion and activation favouring an immunosuppressant profile that contrib-utes to immune homeostasis maintenance at the maternal?foetal interface.