title: Progesterone and VIP cross-talk enhances phagocytosis and anti-inflammatory profile in trophoblast-derived cells.
abstract: Trophoblast cells produce several inmmuneregulators like the Vasoactive Intestinal Peptide (VIP) and P4 targeting multiple circuits, and also display an intese phagocytic ability allowing embryo implantation in a tolerogenic context. Here, we explored whether P4 and VIP- crosstalk modulates trophoblast cell function, focus on the phagocytic ability and the immune homeostasis maintenance. P4 enhanced the phagocytosis in trophoblast-derived cells quantified by the engulfment of latex-beads or eryptotic erythrocytes. P4 and VIP modulated the balance of anti/pro-inflammatory mediators, increasing TGF-β expression, with no changes in IL-1, IL-6, or nitrites production. This modulation was accompained by transcription factor expression changes that could turn on tolerogenic programs represented by increased PPAR-γ and decreased IRF-5 expression. Finally, P4 stimulated VPAC2 expression in trophoblast cells and VPAC2 over-expression enhanced phagocytosis mimicking P4-effect. Therefore, P4 and VIP network enhances the phagocytic ability of trophoblast-derived cells, through a mechanism involving VPAC2 accompained with an anti-inflammatory context.
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Argentina.
authors.forename: Daiana
authors.initials: D
authors.lastname: Vota
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Argentina.
authors.forename: Mariana
authors.initials: M
authors.lastname: Aguero
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Argentina.
authors.forename: Esteban
authors.initials: E
authors.lastname: Grasso
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Argentina.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Hauk
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Argentina.
authors.forename: Lucila
authors.initials: L
authors.lastname: Gallino
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Argentina.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Soczewski
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Argentina.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pérez Leirós
authors.affiliation: Immunopharmacology Laboratory, School of Sciences, University of Buenos Aires, IQUIBICEN-CONICET, Argentina. Electronic address: rramhorst@qb.fcen.uba.ar.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Ramhorst
mesh_terms: D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D010587:Phagocytosis / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology* / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014157:Transcription Factors; D014660:Vasoactive Intestinal Peptide; D011374:Progesterone
keywords: Maternal–placental interface; Phagocytosis; Progesterone; Trophoblast-derived cells; Vasoactive intestinal polypeptide