title: Nuclear factor kappa B activation occurs in the amnion prior to labour onset and modulates the expression of numerous labour associated genes.
abstract: BACKGROUND
  Prior to the onset of human labour there is an increase in the synthesis of prostaglandins, cytokines and chemokines in the fetal membranes, particular the amnion. This is associated with activation of the transcription factor nuclear factor kappa B (NFκB). In this study we characterised the level of NFκB activity in amnion epithelial cells as a measure of amnion activation in samples collected from women undergoing caesarean section at 39 weeks gestation prior to the onset of labour.
  
  
  RESULTS
  We found that a proportion of women exhibit low or moderate NFκB activity while other women exhibit high levels of NFκB activity (n = 12). This activation process does not appear to involve classical pathways of NFκB activation but rather is correlated with an increase in nuclear p65-Rel-B dimers. To identify the full range of genes upregulated in association with amnion activation, microarray analysis was performed on carefully characterised non-activated amnion (n = 3) samples and compared to activated samples (n = 3). A total of 919 genes were upregulated in response to amnion activation including numerous inflammatory genes such cyclooxygenase-2 (COX-2, 44-fold), interleukin 8 (IL-8, 6-fold), IL-1 receptor accessory protein (IL-1RAP, 4.5-fold), thrombospondin 1 (TSP-1, 3-fold) and, unexpectedly, oxytocin receptor (OTR, 24-fold). Ingenuity Pathway Analysis of the microarray data reveal the two main gene networks activated concurrently with amnion activation are i) cell death, cancer and morphology and ii) cell cycle, embryonic development and tissue development.
  
  
  CONCLUSIONS
  Our results indicate that assessment of amnion NFκB activation is critical for accurate sample classification and subsequent interpretation of data. Collectively, our data suggest amnion activation is largely an inflammatory event that occurs in the amnion epithelial layer as a prelude to the onset of labour.
authors.affiliation: Imperial College Parturition Research Group, Institute of Reproduction and Developmental Biology, Imperial College London, London, United Kingdom.
authors.forename: Sheri
authors.initials: S
authors.lastname: Lim
authors.forename: David A
authors.initials: DA
authors.lastname: MacIntyre
authors.forename: Yun S
authors.initials: YS
authors.lastname: Lee
authors.forename: Shirin
authors.initials: S
authors.lastname: Khanjani
authors.forename: Vasso
authors.initials: V
authors.lastname: Terzidou
authors.forename: T G
authors.initials: TG
authors.lastname: Teoh
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Bennett
mesh_terms: D000650:Amnion / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007745:Labor Onset / Q000235:genetics*; D007743:Labor, Obstetric / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism*; D051841:Transcription Factor RelB / Q000378:metabolism*
chemical_list: D016207:Cytokines; D011257:Pregnancy Proteins; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB