title: ATF3 is a negative regulator of inflammation in human fetal membranes.
abstract: Infection and inflammation stimulate pro-inflammatory cytokines, prostaglandins and matrix metalloproteinase (MMP)-9, which play a central role in myometrial contractions and rupture of fetal membranes. In human and mouse immune cells, activating transcription factor 3 (ATF3) is a negative regulator of inflammation. No studies have examined the role of ATF3 in human labour.
  
  
  
  Primary amnion cells were used to determine the effect of interleukin (IL)-1β and the bacterial product fibroblast-stimulating lipopeptide (fsl-1) on ATF3 expression, and the effect of ATF3 siRNA on pro-labour mediators. ATF3 expression was assessed in fetal membranes from non-labouring and labouring women at term and preterm, and after preterm pre-labour rupture of membranes (PPROM).
  
  
  
  IL-1β and fsl-1 significantly increased ATF3 expression. Silencing ATF3 significantly increased IL-1β- or fsl-1-induced expression of pro-inflammatory cytokines (TNF-α, IL-1α, IL-1β, IL-6) and chemokines (IL-8 and monocyte chemoattractant protein-1 (MCP-1)); cyclooxygenase-2 (COX-2) mRNA expression and prostaglandin PGF2αrelease; and MMP-9 expression. ATF3 expression was decreased in fetal membranes with term labour. There was no effect of preterm labour or PPROM on ATF3 expression.
  
  
  
  ATF3 is a negative regulator of inflammation in human fetal membranes; in primary amnion cells, ATF3 expression is induced by IL-1β and fsl-1, and ATF3 silencing further exacerbates the inflammatory response when stimulated with these factors. Subsequently, ATF3 expression is decreased in fetal membranes after term labour and with preterm chorioamnionitis, conditions closely associated with inflammation and infection. Our data suggest that ATF3 may play a role in the terminal processes of human labour and delivery.
authors: Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors: Ratana
authors: R
authors: Lim
authors: Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors: Gillian
authors: G
authors: Barker
authors: Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors: Stella
authors: S
authors: Liong
authors: Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors: Caitlyn
authors: C
authors: Nguyen-Ngo
authors: Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia; Translational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia.
authors: Stephen
authors: S
authors: Tong
authors: Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia; Translational Obstetrics Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia.
authors: Tu'uhevaha
authors: T
authors: Kaitu'u-Lino
authors: Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia. Electronic address: mlappas@unimelb.edu.au.
authors: Martha
authors: M
authors: Lappas
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002821:Chorioamnionitis / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004075:Diglycerides / Q000494:pharmacology; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology; D007743:Labor, Obstetric / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D011247:Pregnancy
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D016207:Cytokines; D004075:Diglycerides; C460864:FSL-1 lipoprotein, synthetic; D053583:Interleukin-1beta; D009842:Oligopeptides
keywords: ATF3; Fetal membranes; Human labour; Infection; Inflammation