title: In vitro progesterone modulation on bacterial endotoxin-induced production of IL-1β, TNFα, IL-6, IL-8, IL-10, MIP-1α, and MMP-9 in pre-labor human term placenta.
abstract: BACKGROUND
  During human pregnancy, infection/inflammation represents an important factor that increases the risk of developing preterm labor. The purpose of this study was to determine if pre-treatment with progesterone has an immunomodulatory effect on human placenta production of endotoxin-induced inflammation and degradation of extracellular matrix markers.
  
  
  METHODS
  Placentas were obtained under sterile conditions from pregnancies delivered at term before the onset of labor by cesarean section. Explants from central cotyledons of 10 human placentas were pre-treated with different concentrations of progesterone (0.01, 01, 1.0 μM) and then stimulated with 1000 ng/mL of LPS of Escherichia coli. Cytokines TNFα, IL-1β, IL-6, IL-8, MIP-1α, IL-10 concentrations in the culture medium were then measured by specific ELISA. Secretion profile of MMP-9 was evaluated by ELISA and zymogram. Statistical differences were determined by one-way ANOVA followed by the appropriate ad hoc test; P < 0.05 was considered statistically significant.
  
  
  RESULTS
  In comparison to the explants incubated with vehicle, the LPS treatment led to a significant increase in the level of all cytokines. In comparison to the explants treated only with LPS, pre-treatment with 0.01-1.0 μM progesterone significantly blunted (73, 56, 56, 75, 25, 48 %) the secretion of TNF-α, IL-1β, IL-6, IL-8, MIP-1α, IL-10, respectively. The MMP-9 induced by LPS treatment was inhibited only with the highest concentration of progesterone. Mifepristone (RU486) blocked the immunosuppressive effect of progesterone.
  
  
  CONCLUSIONS
  The present results support the concept that progesterone could be part of the compensatory mechanism that limits the inflammation-induced cytotoxic effects associated with an infection process during gestation.
authors.affiliation: Inmunobiochemistry Branch, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes", Montes Urales 800, Lomas Virrreyes, Ciudad de Mexico, 11000, Mexico. alejandro_2392@hotmail.com.|Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Estado de Mexico, Ciudad de Mexico, 54700, Mexico. alejandro_2392@hotmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Garcia-Ruíz
authors.affiliation: Inmunobiochemistry Branch, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes", Montes Urales 800, Lomas Virrreyes, Ciudad de Mexico, 11000, Mexico. m.pilar.flores.e@gmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Flores-Espinosa
authors.affiliation: Inmunobiochemistry Branch, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes", Montes Urales 800, Lomas Virrreyes, Ciudad de Mexico, 11000, Mexico. sonic_preciado@hotmail.com.|Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Estado de Mexico, Ciudad de Mexico, 54700, Mexico. sonic_preciado@hotmail.com.
authors.forename: E
authors.initials: E
authors.lastname: Preciado-Martínez
authors.affiliation: Inmunobiochemistry Branch, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes", Montes Urales 800, Lomas Virrreyes, Ciudad de Mexico, 11000, Mexico. bermejol@yahoo.com.mx.
authors.forename: L
authors.initials: L
authors.lastname: Bermejo-Martínez
authors.affiliation: Inmunobiochemistry Branch, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes", Montes Urales 800, Lomas Virrreyes, Ciudad de Mexico, 11000, Mexico. aurora_espnu@yahoo.com.mx.
authors.forename: A
authors.initials: A
authors.lastname: Espejel-Nuñez
authors.affiliation: Inmunobiochemistry Branch, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes", Montes Urales 800, Lomas Virrreyes, Ciudad de Mexico, 11000, Mexico. gpestrad@gmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Estrada-Gutierrez
authors.affiliation: Neonatology Branch, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes", Montes Urales 800, Lomas Virreyes, Ciudad de Mexico, 11000, México. rofmaida@yahoo.com.mx.
authors.forename: R
authors.initials: R
authors.lastname: Maida-Claros
authors.affiliation: Inmunobiochemistry Branch, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes", Montes Urales 800, Lomas Virrreyes, Ciudad de Mexico, 11000, Mexico. arturo_fpliego@yahoo.com.mx.
authors.forename: A
authors.initials: A
authors.lastname: Flores-Pliego
authors.affiliation: Inmunobiochemistry Branch, Instituto Nacional de Perinatología "Isidro Espinosa de los Reyes", Montes Urales 800, Lomas Virrreyes, Ciudad de Mexico, 11000, Mexico. v.zagaclavellina@gmail.com.|Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Estado de Mexico, Ciudad de Mexico, 54700, Mexico. v.zagaclavellina@gmail.com.
authors.forename: Veronica
authors.initials: V
authors.lastname: Zaga-Clavellina
mesh_terms: D000328:Adult; D002585:Cesarean Section; D054405:Chemokine CCL3 / Q000096:biosynthesis; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009924:Organ Culture Techniques; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D054405:Chemokine CCL3; D004731:Endotoxins; C508609:IL10 protein, human; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D011374:Progesterone; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9