title: Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are increased after labour in foetal membranes and myometrium and are essential for TNF-α-induced expression of pro-labour mediators.
abstract: OBJECTIVE
  Inflammation is commonly associated with preterm birth. In non-gestational tissues, the cellular inhibitor of apoptosis protein (cIAP) 1 and 2, independent of their role in apoptosis, have emerged as important regulators of inflammation. There is, however, no data on the effect of human labour on the expression of cIAPs in human gestational tissues, or on their role in modulating TNF-α induced inflammation.
  
  
  METHODS
  Myometrium and fetal membranes and myometrium were obtained from term non-labouring and labouring fetal membranes and myometrium. Fetal membranes were also obtained from preterm non-labouring and labouring fetal membranes with and without histological chorioamnionitis. The effect of cIAP1 and cIAP2 knockdown by siRNA in myometrial primary cells on pro-labour mediators was also determined.
  
  
  RESULTS
  cIAP1 and cIAP2 expression was significantly higher in fetal membranes and myometrium after spontaneous labour, in preterm fetal membranes with infection, and with LPS and TNF-α. cIAP2 expression was also higher in fetal membranes after spontaneous preterm labour when compared to non-labouring tissues. Knockdown of cIAP1 and cIAP2 in primary myometrial cells significantly decreased TNF-α induced expression and secretion of pro-inflammatory cytokines (IL-6 and IL-8); cyclooxygenase (COX)-2 expression and subsequent release of the prostaglandin PGE2 ; the expression and secretion of MMP-9; and NF-κB transcriptional activity.
  
  
  CONCLUSIONS
  cIAP1 and cIAP2 are increased after labour in fetal membranes and myometrium and are involved in TNF-α induced-expression of pro-labour mediators. Thus, cIAP1 and cIAP2 represent novel therapeutic targets for the prevention of spontaneous preterm birth.
authors.affiliation: Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, VIC, Australia; Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, VIC, Australia.
authors.forename: Martha
authors.initials: M
authors.lastname: Lappas
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009215:Myometrium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D007752:Obstetric Labor, Premature / Q000378:metabolism; D011247:Pregnancy; D047929:Term Birth / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D055815:Young Adult
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone
keywords: Foetal membranes; human labour; inflammation; inhibitor of apoptosis; myometrium