Nuclear factor kappa B activation occurs in the amnion prior to labour onset and modulates the expression of numerous labour associated genes

• Published in: PloS one Vol. 7; no. 4; p. e34707
• Main Authors: Lim, Sheri, MacIntyre, David A, Lee, Yun S, Khanjani, Shirin, Terzidou, Vasso, Teoh, T G, Bennett, Phillip R
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.04.2012; Public Library of Science (PLoS)
• Subjects: Amnion; Amnion - metabolism; Androgens; Angiogenesis; Apoptosis; Biology; Cancer; Cell activation; Cell cycle; Cell death; Cell growth; Cell Nucleus - metabolism; Chemokines; COX-2 inhibitors; Cyclooxygenase-2; Cytokines; Cytokines - genetics; Cytokines - metabolism; Cytology; Data interpretation; Deoxyribonucleic acid; Developmental biology; Dimers; DNA; DNA microarrays; Embryogenesis; Embryonic development; Embryonic growth stage; Epidermal growth factor; Epithelial cells; Female; Fetuses; Gene expression; Gene Expression Regulation; Gene Regulatory Networks; Genes; Genetic research; Gestation; Humans; Inflammation; Interleukin; Interleukin 1; Interleukin 1 receptors; Interleukin 8; Interleukins; Kinases; Labor Onset - genetics; Labor, Obstetric - genetics; Medicine; Membranes; Metabolism; Metabolites; NF-κB protein; Oligonucleotide Array Sequence Analysis; Oxytocin; Polypeptides; Pregnancy; Pregnancy - metabolism; Pregnancy Proteins - genetics; Pregnancy Proteins - metabolism; Prostaglandins; Prostate cancer; Protein Binding; Protein folding; Proteins; Signal Transduction; Thrombospondin; Transcription activation; Transcription Factor RelA - metabolism; Transcription Factor RelB - metabolism; Transcription factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0034707

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. 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. 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.