title: Cellular inhibitors of apoptosis (cIAP) 1 and 2 are increased in placenta from obese pregnant women.
abstract: BACKGROUND
  Independent of their role in apoptosis, cellular inhibitors of apoptosis (cIAP) 1 and 2, have emerged as regulators of inflammation. Obesity in pregnancy is characterised by maternal and placental inflammation. Thus, the aim of this study was to determine the effect of maternal obesity and pro-inflammatory mediators on cIAP expression in human placenta.
  
  
  METHODS
  The expression of cIAP was assessed in human placenta from lean (n = 15) and obese (n = 14) patients by qRT-PCR and Western blotting. Primary trophoblast cells were used to determine the effect of pro-inflammatory cytokines on cIAP expression, and the effect of cIAP siRNA on pro-inflammatory cytokines.
  
  
  RESULTS
  cIAP1 and cIAP2, gene and protein expression were significantly higher in placenta from women with pre-existing maternal obesity compared to placenta form lean women. Additionally, bacterial endotoxin LPS and the pro-inflammatory cytokines tumour necrosis factor (TNF)-α and interleukin (IL)-1β significantly increased the expression of both cIAP1 and cIAP2 in primary trophoblast cells isolated from human term placenta. Knockdown of cIAP1 or cIAP2 in human primary trophoblast cells significantly decreased TNF-α induced expression and secretion of pro-inflammatory cytokines IL-6 and IL-8 and of matrix metalloproteinase (MMP)-9.
  
  
  CONCLUSIONS
  cIAP1 and cIAP2 expression is increased in placenta from women with pre-existing maternal obesity and in response to treatment with pro-inflammatory cytokines. Functional studies in placental trophoblast cells revealed that cIAPs are involved in TNF-α induced-expression of pro-inflammatory cytokines. Given the central role of pro-inflammatory cytokines in placental nutrient transport, this data suggest that cIAP1 and cIAP2 may play a role in fetal growth and development.
authors.affiliation: Mercy Perinatal Research Centre, Mercy Hospital for Women, Heidelberg, Victoria, Australia; Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia. Electronic address: mlappas@unimelb.edu.au.
authors.forename: M
authors.initials: M
authors.lastname: Lappas
mesh_terms: D000328:Adult; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology; D009765:Obesity / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D044767:Ubiquitin-Protein Ligases
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases
keywords: Inflammation; Obesity; Placenta; cIAP1; cIAP2