title: Contribution of vasoactive intestinal peptide to immune homeostasis in trophoblast-maternal leukocyte interaction under LPS stimulation.
abstract: OBJECTIVE
  The maternal-fetal interface is a unique immunological site that generates an adequate microenvironment during pregnancy, recognizing and eliminating infections and tolerating the trophoblast/placenta unit. For that purpose, trophoblast cells display several tolerogenic mechanisms to allow fetal survival, such as production of the neuropeptide vasoactive intestinal peptide (VIP). Here we investigated the contribution of VIP to maintain homeostasis at the maternal-placental interface under lipopolysaccharide (LPS) stimulation.
  
  
  METHODS
  We performed cocultures between trophoblast cells (Swan-71 cell line) and maternal leukocytes obtained from fertile women as an in vitro model of maternal-placental interaction, and we focused on the effects of LPS on the modulation of VIP and their receptors (VPAC1 and VPAC2).
  
  
  RESULTS
  VIP could prevent the upregulation of IL-6, MCP-1, and nitrite production and maintain the production of IL-10 and TGF-β under LPS (10 µg/ml) stimulation after 48 h of coculture. To gain deeper insight into the mechanisms of how VIP could contribute to a tolerogenic microenvironment even in the presence of LPS, we investigated VIP production by maternal leukocytes and observed a significant increase in the frequency of CD4+VIP+ cells after interaction with Swan-71 cells in the presence of LPS. LPS increased VIP and inducible receptor VPAC2 expression directly on trophoblast cells in a dose- and time-dependent manner.
  
  
  CONCLUSIONS
  The present results suggest that VIP might act as an additional homeostatic mechanism during early stages at the maternal-placental interface to control exacerbated inflammatory responses such as the ones observed in intrauterine infections.
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires and IQUIBICEN-CONICET (National Research Council of Science and Technology, CONICET), Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Fraccaroli
authors.forename: Esteban
authors.initials: E
authors.lastname: Grasso
authors.forename: Vanesa
authors.initials: V
authors.lastname: Hauk
authors.forename: Marta
authors.initials: M
authors.lastname: Cortelezzi
authors.forename: Claudia
authors.initials: C
authors.lastname: Pérez Leirós
authors.forename: Rosanna
authors.initials: R
authors.lastname: Ramhorst
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009573:Nitrites / Q000378:metabolism; D011247:Pregnancy; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014327:Trophoblasts / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D009573:Nitrites; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D016212:Transforming Growth Factor beta; D014660:Vasoactive Intestinal Peptide