Nuclear Factor Kappa B Activation Occurs in the Amnion Prior to Labour Onset and Modulates the Expression of Numerous Labour Associated Genes 英文参考文献.docVIP
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Nuclear Factor Kappa B Activation Occurs in the Amnion Prior to Labour Onset and Modulates the Expression of Numerous Labour Associated Genes 英文参考文献
NuclearFactorKappaBActivationOccursintheAmnion
PriortoLabourOnsetandModulatestheExpressionof
NumerousLabourAssociatedGenes
SheriLim1,DavidA.MacIntyre1,YunS.Lee1,ShirinKhanjani1,VassoTerzidou1,T.G.Teoh2,
PhillipR.Bennett1*
1ImperialCollegeParturitionResearchGroup,InstituteofReproductionandDevelopmentalBiology,ImperialCollegeLondon,London,UnitedKingdom,2Departmentof
ObstetricsandGynaecology,St.Mary’sHospital,London,UnitedKingdom
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 (NFkB). In this study we characterised the level of NFkB activity in amnion epithelial cells as a
measureofamnionactivationinsamplescollectedfromwomenundergoingcaesareansectionat39weeksgestationprior
totheonsetoflabour.
Methodology/PrincipalFindings:WefoundthataproportionofwomenexhibitlowormoderateNFkBactivitywhileother
womenexhibithighlevelsofNFkBactivity(n=12).Thisactivationprocessdoesnotappeartoinvolveclassicalpathwaysof
NFkBactivationbutratheriscorrelatedwithanincreaseinnuclearp65-Rel-Bdimers.Toidentifythefullrangeofgenes
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
responsetoamnionactivationincludingnumerousinflammatorygenessuchcyclooxygenase-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
developmentandtissuedevelopment.
Conclusions/Significance: Our resul
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