title: Amniotic Fluid Soluble Myeloid Differentiation-2 (sMD-2) as Regulator of Intra-amniotic Inflammation in Infection-induced Preterm Birth.
abstract: OBJECTIVE
  TLR4 mediates host responses to pathogens through a mechanism that involves protein myeloid differentiation-2 (MD-2) and its soluble form sMD-2. The role of sMD2 in intra-amniotic inflammation-induced preterm birth has not been previously explored.
  
  
  METHODS
  Human amniotic fluid (AF) sMD-2 was studied by Western blotting in 152 AF samples of patients who had an amniocentesis to rule-out infection (yes infection, n = 50; no infection, n = 50) or women with normal pregnancy outcome (second trimester genetic karyotyping, n = 26; third trimester lung maturity testing, n = 26). Histological localization and mRNA expression of MD2 in fetal membranes were studied by immunohistochemistry and RT-PCR. The ability of fetal membrane to release sMD-2 and inflammatory cytokines was studied in vitro.
  
  
  RESULTS
  Human AF contains three sMD-2 proteoforms whose levels of expression were lower at term. Intra-amniotic infection upregulated sMD-2. MD-2 mRNA and immunohistochemistry findings concurred. In vitro, LPS and monensin increased, while cycloheximide decreased sMD-2 production. Recombinant sMD-2 modulated TNF-α and IL-6 levels in a dose- and time-dependent fashion.
  
  
  CONCLUSIONS
  sMD2 proteoforms are constitutively present in human AF. The intensity of the intra-amniotic inflammatory response to bacteria or perhaps to other TLR4 ligands may be facilitated through synthesis and release of sMD2 by the amniochorion.
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH, USA.|Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Antonette T
authors.initials: AT
authors.lastname: Dulay
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH, USA.|Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Guomao
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Oliver
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Sonya S
authors.initials: SS
authors.lastname: Abdel-Razeq
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Lydia L
authors.initials: LL
authors.lastname: Shook
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Mert O
authors.initials: MO
authors.lastname: Bahtiyar
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH, USA.|Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.|Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000276:immunology* / Q000382:microbiology; D001424:Bacterial Infections / Q000276:immunology* / Q000473:pathology; D002823:Chorion / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051218:Lymphocyte Antigen 96 / Q000276:immunology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D047928:Premature Birth / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C495377:LY96 protein, human; D051218:Lymphocyte Antigen 96
keywords: Bacteria; early-onset neonatal sepsis; fetal membranes; fetus; infection; inflammation; pregnancy