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

D. PAPARINI; S. GORI; E. GRASSO; W. SCORDO; G. CALO; C. PÉREZ LEIRÓS; R. RAMHORST; G. SALAMONE

ACTA PHYSIOLOGICA

WILEY-BLACKWELL PUBLISHING, INC

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

1748-1708

Maternal antigen presenting cells attracted to the pregnant uterus interact with trophoblast cells and modulate their functional profile to favor 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 cells. 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 cell-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 favoring an immunosuppressant profile that contributes to immune homeostasis maintenance at the maternal-fetal interface.