title: Autophagy, which is decreased in labouring fetal membranes, regulates IL-1β production via the inflammasome.
abstract: BACKGROUND
  IL-1β plays a vital role in the terminal processes of human labour and delivery. Inflammasome activation is required to process pro IL-1β to an active, secreted molecule. Recent studies have shown that autophagy regulates IL-1β via the inflammasome. The aims were to determine the effect of (i) human spontaneous term and preterm labour on the expression of autophagy proteins in fetal membranes; and (ii) autophagy inhibition on IL-1β release.
  
  
  METHODS
  Fetal membranes, from term and preterm, were obtained from non-labouring and labouring women. Tissue explants were used to determine the effect of inhibition of autophagy on IL-1β secretion.
  
  
  RESULTS
  Expression of the autophagy proteins Beclin-1, Atg3, Atg5, Atg7, Atg12, Atg16L1 were lower after spontaneous term labour. Beclin-1 and Atg7 expression were lower after spontaneous preterm labour. Beclin-1, Atg3, and Atg7 expression were lower after preterm pre-labour rupture of membranes (PPROM) compared to preterm with intact membranes. LC3B-I expression was higher after spontaneous term and preterm labour and with PPROM; there was no difference in LC3B-II expression between the two groups. The autophagy inhibitor LY290042 increased IL-1β secretion in the presence of bacterial endotoxin LPS; IL-1β secretion was ameliorated in the presence inflammasome inhibitors.
  
  
  CONCLUSIONS
  Autophagy is decreased in fetal membranes after spontaneous labour and delivery, and PPROM. Inhibition of autophagy regulates the secretion of IL-1β via inflammasome activation. IL-1β is a major contributor to the pathophysiology of spontaneous preterm birth. Therefore activation of autophagy may be a potential therapeutic mechanism to delay or prevent infection-induced preterm birth.
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.
authors.forename: Amelia
authors.initials: A
authors.lastname: Brickle
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.
authors.forename: Ha Thi
authors.initials: HT
authors.lastname: Tran
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.
authors.forename: Ratana
authors.initials: R
authors.lastname: Lim
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.
authors.forename: Stella
authors.initials: S
authors.lastname: Liong
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: Martha
authors.initials: M
authors.lastname: Lappas
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D000071183:Autophagy-Related Proteins; D000071186:Beclin-1; D020170:Caspase 1 / Q000378:metabolism; D005321:Extraembryonic Membranes / Q000378:metabolism*; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D007743:Labor, Obstetric / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D011247:Pregnancy; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism
chemical_list: C502778:ATG5 protein, human; D051017:Apoptosis Regulatory Proteins; D000071187:Autophagy-Related Protein 5; D000071183:Autophagy-Related Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D058847:Inflammasomes; D053583:Interleukin-1beta; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D044763:Ubiquitin-Conjugating Enzymes; D020170:Caspase 1; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; C455621:ATG3 protein, human
keywords: Autophagy; Fetal membranes; Human labour; Inflammasome; Membrane rupture