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Acetylcholine contributes to control the physiological inflammatory response during the peri‐implantation period
Author(s) -
Paparini D.,
Gori S.,
Grasso E.,
Scordo W.,
Calo G.,
Pérez Leirós C.,
Ramhorst R.,
Salamone G.
Publication year - 2015
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12494
Subject(s) - trophoblast , cytotrophoblast , acetylcholine , muscarinic acetylcholine receptor , cholinergic , microbiology and biotechnology , immune system , medicine , biology , endocrinology , muscarinic acetylcholine receptor m3 , receptor , immunology , placenta , pregnancy , fetus , genetics
Background Maternal antigen‐presenting cells attracted to the pregnant uterus interact with trophoblast cells and modulate their functional profile to favour immunosuppressant responses. Non‐neuronal cholinergic system is expressed in human cytotrophoblast cells and in immune cells with homeostatic regulatory functions. Aim The aim of this work was to evaluate whether non‐neuronal acetylcholine conditions maternal monocyte and DC migration and activation profiles. Methods We used an in vitro model resembling maternal–placental interface represented by the co‐culture of human trophoblast cells (Swan‐71 cell line) and monocytes or DC. Results When cytotrophoblast cells were treated with neostigmine (Neo) to concentrate endogenous acetylcholine levels, monocyte migration was increased. In parallel, high levels of IL‐10 and decreased levels of TNF‐α were observed upon interaction of maternal monocytes with trophoblast cells. This effect was synergized by Neo and was prevented by atropine, a muscarinic acetylcholine receptor antagonist. Similarly, trophoblast cells increased the migration of DC independently of Neo treatment; however, enhanced IL‐10 and MCP‐1 synthesis in trophoblast–DC co‐cultures with no changes in TNF‐α and IL‐6 was observed. In fact, there were no changes in HLA‐DR, CD86 or CD83 expression. Finally, trophoblast cells treated with Neo increased the expression of two antigen‐presenting cells attracting chemokines, MCP‐1, MIP‐1α and RANTES through muscarinic receptors, and it was prevented by atropine. Conclusions Our present results support a novel role of acetylcholine synthesized by trophoblast cells to modulate antigen‐presenting cell migration and activation favouring an immunosuppressant profile that contributes to immune homeostasis maintenance at the maternal–foetal interface.