title: Progesterone elicits an inhibitory effect upon LPS-induced innate immune response in pre-labor human amniotic epithelium.
abstract: OBJECTIVE
  Infection of human fetal membranes elicits secretion of pro-inflammatory modulators through its innate immune capacities. We investigated the effect of lipopolysacharide (LPS) and progesterone (P4) upon expression of TLR-4/MyD88, TNFα, IL-6, IL-8, IL-10, and HBD2 on the human amniotic epithelium.
  
  
  METHODS
  Explants of the human amniotic epithelium were pre-treated with 0.01, 0.1, and 1.0 μM of P4; then cotreated with 1000 ng/mL LPS. TLR-4 was immuno-detected, and concentrations of MyD88, TNFα, IL-6, IL-8, IL-10, and HBD2 were quantified by ELISA.
  
  
  RESULTS
  P4 significantly reduced the expression of LPS-induced TLR-4/MyD88. LPS increased the concentrations of TNFα, IL-6, IL-8, IL-10, and HBD2 by factors of 30-, eight, three, three, and fivefold, respectively. P4 at 1.0 μM was the most effective dose to blunt the secretion of TNFα, IL-6, and HBD-2. RU-486 blocks the effect of P4.
  
  
  CONCLUSIONS
  P4 inhibited LPS-induced TLR-4/MyD88 and pro-inflammatory factors in the human amniotic epithelium. These results could explain partially how P4 can protect the amniotic region of fetal membranes and generate a compensatory mechanism that limits the secretion of pro-inflammatory modulators, which could jeopardize the immune privilege during pregnancy.
authors.affiliation: Department of Cell Biology, Instituto Nacional de Perinatología 'Isidro Espinosa de los Reyes', Mexico City, Mexico; Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Pilar
authors.initials: P
authors.lastname: Flores-Espinosa
authors.forename: Montzerrat
authors.initials: M
authors.lastname: Pineda-Torres
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Vega-Sánchez
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Estrada-Gutiérrez
authors.forename: Aurora
authors.initials: A
authors.lastname: Espejel-Nuñez
authors.forename: Arturo
authors.initials: A
authors.lastname: Flores-Pliego
authors.forename: Rolando
authors.initials: R
authors.lastname: Maida-Claros
authors.forename: Yuriria
authors.initials: Y
authors.lastname: Paredes-Vivas
authors.forename: Iyari
authors.initials: I
authors.lastname: Morales-Méndez
authors.forename: Irma
authors.initials: I
authors.lastname: Sosa-González
authors.forename: Angel
authors.initials: A
authors.lastname: Chávez-Mendoza
authors.forename: Verónica
authors.initials: V
authors.lastname: Zaga-Clavellina
mesh_terms: D000650:Amnion / Q000166:cytology*; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004848:Epithelium / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D015735:Mifepristone / Q000494:pharmacology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; C106641:DEFB4A protein, human; D006727:Hormone Antagonists; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D023083:beta-Defensins; D015735:Mifepristone; D011374:Progesterone
keywords: Chorioamnionitis; TLR-4; human amniotic epithelium; inflammation; innate immunity; progesterone