title: Activation of AMPK in human fetal membranes alleviates infection-induced expression of pro-inflammatory and pro-labour mediators.
abstract: BACKGROUND
  In non-gestational tissues, the activation of adenosine monophosphate (AMP)-activated kinase (AMPK) is associated with potent anti-inflammatory actions. Infection and/or inflammation, by stimulating pro-inflammatory cytokines and matrix metalloproteinase (MMP)-9, play a central role in the rupture of fetal membranes. However, no studies have examined the role of AMPK in human labour.
  
  
  METHODS
  Fetal membranes, from term and preterm, were obtained from non-labouring and labouring women, and after preterm pre-labour rupture of membranes (PPROM). AMPK activity was assessed by Western blotting of phosphorylated AMPK expression. To determine the effect of AMPK activators on pro-inflammatory cytokines, fetal membranes were pre-treated with AMPK activators then stimulated with bacterial products LPS and flagellin or viral dsDNA analogue poly(I:C). Primary amnion cells were used to determine the effect of AMPK activators on IL-1β-stimulated MMP-9 expression.
  
  
  RESULTS
  AMPK activity was decreased with term labour. There was no effect of preterm labour. AMPK activity was also decreased in preterm fetal membranes, in the absence of labour, with PROM compared to intact membranes. AMPK activators AICAR, phenformin and A769662 significantly decreased IL-6 and IL-8 stimulated by LPS, flagellin and poly(I:C). Primary amnion cells treated with AMPK activators significantly decreased IL-1β-induced MMP-9 expression.
  
  
  CONCLUSIONS
  The decrease in AMPK activity in fetal membranes after spontaneous term labour and PPROM indicates an anti-inflammatory role for AMPK in human labour and delivery. The use of AMPK activators as possible therapeutics for threatened preterm labour would be an exciting future avenue of research.
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: R
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: G
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. Electronic address: mlappas@unimelb.edu.au.
authors: M
authors: M
authors: Lappas
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D002821:Chorioamnionitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D005321:Extraembryonic Membranes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005408:Flagellin / Q000633:toxicity; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007743:Labor, Obstetric / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000633:toxicity; D007752:Obstetric Labor, Premature / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010929:Placentation; D011247:Pregnancy; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D046509:Tissue Culture Techniques; D051193:Toll-Like Receptors / Q000819:agonists / Q000378:metabolism
chemical_list: D020536:Enzyme Activators; D018836:Inflammation Mediators; D008024:Ligands; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; C433788:lipopolysaccharide, E. coli O26-B6; D005408:Flagellin; D055372:AMP-Activated Protein Kinases; C526180:PRKAA1 protein, human
keywords: AMPK; Fetal membranes; Human labour; Inflammation