title: Placental TLR/NLR expression signatures are altered with gestational age and inflammation.
abstract: OBJECTIVE
  To quantify changes in placental expression of Toll-like receptors (TLRs) and nuclear oligomerization domain (NOD)-like receptors (NLRs) gene with (1) advancing gestational age (GA) and (2) exposure to chorioamnionitis (CA) and preterm premature rupture of membrane (PPROM).
  
  
  METHODS
  Placental tissue was collected at the time of birth from 83 subjects with live birth pregnancies from 24- to 40-week gestation between 2009 and 2013. Real-time RT-PCR analysis of 13 TLR/NLR genes involved in bacterial sensing was performed using specific probes.
  
  
  RESULTS
  Of 83 patients enrolled, 61 were preterm (<37 weeks). 23 (27%) had evidence of CA; and 33 (39.8%) had PPROM. 15 (18%) had both CA and PPROM (CP). 42 (50%) had neither CA nor PPROM (C/P). Only RIPK2 (p = 0.0025) and TLR4 (p = 0.0005) were found to increase progressively with GA. We found significant changes in TLR5 (p = 0.01) with CA, NFKBIA (p = 0.016) with PPROM, NKKBIA (p = 0.003), and NFKB1 (p = 0.009) with CA and PPROM.
  
  
  CONCLUSIONS
  RIPK2 (mediator of NOD-dependent NF-kB signaling) and TLR4 progressively increased with GA. We speculate this upregulation may be involved in initiating labor and delivery at term. Increase in NFKBIA seen in PPROM and CA might represent a counter regulatory mechanism to decrease inflammation in these conditions. This study provides new information on relationships between GA, CA/PPROM, and TLR/NLR signaling in the placenta.
authors.affiliation: a Division of Neonatology, Hurley Medical Center , Flint, MI , USA.
authors.forename: Navin
authors.initials: N
authors.lastname: Kumar
authors.affiliation: b Division of Neonatology, Clinical Center, University of Florida Health at Jacksonville , Jacksonville, FL , USA.
authors.forename: Padma
authors.initials: P
authors.lastname: Nandula
authors.affiliation: c Division of Neonatology, Children's Mercy Hospital , Kansas City, MO , USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Menden
authors.affiliation: d Department of Pathology, Medical College of Wisconsin and Children's Hospital of Wisconsin , Milwaukee, WI , USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Jarzembowski
authors.affiliation: c Division of Neonatology, Children's Mercy Hospital , Kansas City, MO , USA.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Sampath
mesh_terms: D002821:Chorioamnionitis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005865:Gestational Age; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D000070576:NLR Proteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D016328:NF-kappa B; D000070576:NLR Proteins; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C506253:RIPK2 protein, human; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2
keywords: Placenta; TLR/NLR; innate immunity; ontogeny