title: Intra-amniotic infection upregulates neutrophil gelatinase-associated lipocalin (NGAL) expression at the maternal-fetal interface at term: implications for infection-related preterm birth.
abstract: OBJECTIVE
  Neutrophil gelatinase-associated lipocalin (NGAL) is a ubiquitous lipocalin that serves as a critical component of innate immunity and a transport shuttle for numerous substances (retinoids, arachidonic acid, prostaglandins, fatty acids, steroids, iron, and MMPs). Despite the well-documented association between intra-amniotic infection/inflammation (IAI) and preterm birth, NGAL expression in the uterus has not previously been examined. This study investigates NGAL expression at the maternal-fetal interface in vivo and in vitro.
  
  
  METHODS
  Neutrophil gelatinase-associated lipocalin expression in term placenta with/without IAI was examined by immunohistochemistry. Trophoblast and decidual stromal cells were retrieved from elective cesarean, purified, and depleted of leukocytes. On days 1 (cytotrophoblast cells) and 4 (syncytiotrophoblast), cells were stimulated with/without interleukin 1β (IL-1β; 1 ng/mL), tumor necrosis factor α (TNF-α; 1 ng/mL), or lipopolysaccharide (LPS; 1 μg/mL). Neutrophil gelatinase-associated lipocalin messenger RNA (mRNA) and protein expression were measured by immunocytochemistry/Western blot and RT-qPCR, respectively.
  
  
  RESULTS
  Under basal conditions, NGAL is expressed in trophoblast, but not decidua. Trophoblast NGAL is significantly upregulated in tissues with evidence of IAI vs controls. NGAL expression was increased after stimulation with all 3 pro-inflammatory mediators in day 1 (cytotrophoblast) but not day 4 cells (syncytiotrophoblast). IL-1β and TNF-α (not LPS) upregulated NGAL gene expression in cytotrophoblast (not syncytiotrophoblast) cells.
  
  
  CONCLUSIONS
  Intra-amniotic infection/inflammation is associated with increased expression of NGAL in trophoblast tissues in vivo. IL-1β, TNF-α, and LPS stimulated NGAL in cytotrophoblast cells (not syncytiotrophoblast and decidua) in vitro. These data suggest that, in keeping with its role as a mediator of innate immunity, NGAL may have a central role to play in IAI-induced preterm birth.
authors.affiliation: Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Serkalem
authors.initials: S
authors.lastname: Tadesse
authors.forename: Guoyang
authors.initials: G
authors.lastname: Luo
authors.forename: Joong Shin
authors.initials: JS
authors.lastname: Park
authors.forename: Byoung Jae
authors.initials: BJ
authors.lastname: Kim
authors.forename: Victoria V
authors.initials: VV
authors.lastname: Snegovskikh
authors.forename: Ting
authors.initials: T
authors.lastname: Zheng
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Hodgson
authors.forename: Felice
authors.initials: F
authors.lastname: Arcuri
authors.forename: Paolo
authors.initials: P
authors.lastname: Toti
authors.forename: Chirag R
authors.initials: CR
authors.lastname: Parikh
authors.forename: Seth
authors.initials: S
authors.lastname: Guller
authors.forename: Errol R
authors.initials: ER
authors.lastname: Norwitz
mesh_terms: D002821:Chorioamnionitis / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007234:Infant, Premature; D054834:Lipocalins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D011247:Pregnancy; D047928:Premature Birth / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D054834:Lipocalins