title: IL-10 modulates placental responses to TLR ligands.
abstract: OBJECTIVE
  Intra-uterine infections increase production of pro-inflammatory cytokines. It is unclear whether different infectious agents determine the relative expression of pro-and anti-inflammatory cytokines.
  
  
  METHODS
  We compared the placental inflammatory response induced by bacterial lipopolysaccharide (LPS, endotoxin from Gram-negative bacteria) with those induced by lipoteichoic acid (LTA, a cell wall component of Gram-positive bacteria). Placental explants from term delivery were treated with either LPS or LTA, in the presence or absence of IL-10, for 24 hrs. Cytokines, prostaglandin E(2) (PGE(2)) production and cyclo-oxygenase-2 (COX-2) expression were quantified.
  
  
  RESULTS
  Both LTA and LPS significantly induced several cytokines with LPS eliciting more potent effects. IL-6 and IL-8 were induced to comparable levels in response to both LTA and LPS whereas monocyte chemotactic protein-1 (MCP-1) production was induced more by LTA, demonstrating a differential placental response to a specific toll-like receptor (TLR) ligand. IL-10 treatment significantly reduced most pro-inflammatory cytokines as well as PGE(2) induced by both LPS and LTA. Interestingly, IL-10 down-regulated LTA-mediated MCP1 induction, but not that mediated by LPS. Moreover, IL-10 was more effective in down-regulating PGE(2) after LPS- when compared with LTA stimulation.
  
  
  CONCLUSIONS
  Our results demonstrate that placental exposure to LTA and LPS appear to trigger distinct cytokine responses that can be modulated by IL-10.
authors.affiliation: Department of Pediatrics-Neonatology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Bayraktar
authors.forename: Morgan
authors.initials: M
authors.lastname: Peltier
authors.forename: Anna
authors.initials: A
authors.lastname: Vetrano
authors.forename: Yuko
authors.initials: Y
authors.lastname: Arita
authors.forename: Ellen
authors.initials: E
authors.lastname: Gurzenda
authors.forename: Ansamma
authors.initials: A
authors.lastname: Joseph
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kazzaz
authors.forename: Surendra
authors.initials: S
authors.lastname: Sharma
authors.forename: Nazeeh
authors.initials: N
authors.lastname: Hanna
mesh_terms: D018932:Chemokine CCL2 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D009924:Organ Culture Techniques; D010920:Placenta / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D013682:Teichoic Acids / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D051193:Toll-Like Receptors / Q000276:immunology
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D013682:Teichoic Acids; D051193:Toll-Like Receptors; D016753:Interleukin-10; C009900:lipoteichoic acid; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone