title: Acetylcholine contributes to control the physiological inflammatory response during the peri-implantation period.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, IQUIBICEN-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: D
authors.initials: D
authors.lastname: Paparini
authors.affiliation: Instituto de Medicina Experimental-IMEX-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: S
authors.initials: S
authors.lastname: Gori
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, IQUIBICEN-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: E
authors.initials: E
authors.lastname: Grasso
authors.affiliation: Servicio de Medicina Transfusional, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: W
authors.initials: W
authors.lastname: Scordo
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, IQUIBICEN-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Calo
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, IQUIBICEN-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Pérez Leirós
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, IQUIBICEN-CONICET, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: R
authors.initials: R
authors.lastname: Ramhorst
authors.affiliation: Instituto de Medicina Experimental-IMEX-CONICET, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: G
authors.initials: G
authors.lastname: Salamone
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D002469:Cell Separation / Q000379:methods; D018920:Coculture Techniques; D010064:Embryo Implantation / Q000276:immunology*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology; D010920:Placenta / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology* / Q000276:immunology
chemical_list: D000109:Acetylcholine
keywords: dendritic cells; monocytes; non-neuronal acetylcholine; trophoblast cells