title: High Mobility Group-Box 1 (HMGB1) levels are increased in amniotic fluid of women with intra-amniotic inflammation-determined preterm birth, and the source may be the damaged fetal membranes.
abstract: BACKGROUND
  High Mobility Group Box-1 (HMGB1) is considered a prototype alarmin molecule. Upon its extracellular release, HMGB1 engages pattern recognition receptors and the Receptor for Advanced Glycation End-products (RAGE) followed by an outpouring of inflammatory cytokines, including interleukin (IL)-6.
  
  
  METHODS
  We assayed the amniotic fluid (AF) levels of HMGB1 and IL-6 in 255 women that either had a normal pregnancy outcome or delivered preterm. Immunohistochemistry on fetal membranes was used for cellular localization and validation of immunoassay findings. HMGB1 also was analyzed in amniochorion tissue explants subjected to endotoxin.
  
  
  RESULTS
  AF HMGB1 levels are not gestational age regulated but are increased in women with intra-amniotic inflammation and preterm birth. The likely source is the damaged amniochorion, as demonstrated by immunohistochemistry and explant experiments.
  
  
  CONCLUSIONS
  Our research supports a role for HMGB1 in the inflammatory response leading to preterm birth. As a delayed phase cytokine, in utero exposure to elevated AF HMGB1 levels may have an impact on the newborn beyond the time of birth.
authors.affiliation: Department of Ob./Gyn. & Reproductive Sciences, Yale University School of Medicine, United States.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Baumbusch
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, United States.
authors.forename: Catalin S
authors.initials: CS
authors.lastname: Buhimschi
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, United States.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Oliver
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43215, United States.
authors.forename: Guomao
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, United States.
authors.forename: Stephen
authors.initials: S
authors.lastname: Thung
authors.affiliation: Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH 43210, United States.
authors.forename: Kara
authors.initials: K
authors.lastname: Rood
authors.affiliation: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH 43215, United States; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH 43215, United States. Electronic address: irina.buhimschi@nationwidechildrens.org.
authors.forename: Irina A
authors.initials: IA
authors.lastname: Buhimschi
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000378:metabolism*; D002821:Chorioamnionitis / Q000378:metabolism* / Q000503:physiopathology; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005865:Gestational Age; D024243:HMGB1 Protein / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D007118:Immunoassay; D007150:Immunohistochemistry; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D011247:Pregnancy; D047928:Premature Birth / Q000378:metabolism* / Q000503:physiopathology; D000067759:Receptor for Advanced Glycation End Products / Q000032:analysis; D055815:Young Adult
chemical_list: D024243:HMGB1 Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000067759:Receptor for Advanced Glycation End Products
keywords: Alarmins; Amniochorion; DAMPs; Endokines; Innate immunity; Preterm birth