title: Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep.
abstract: BACKGROUND
  Fetal lung maturation occurs after both maternal corticosteroid administration and chorioamnionitis. The effectors of this antenatally-induced lung maturation are not understood. Matrix metalloproteinases (MMPs) 2 and 9 are type-IV collagenases that can degrade alveolar basement membranes.
  
  
  OBJECTIVE
  We hypothesized that the structural changes of lung maturation by both antenatal corticosteroid treatment and chorioamnionitis would be associated with increases in these MMPs.
  
  
  METHODS
  64 pregnant ewes were randomly assigned to one of four treatment groups: intra-amniotic injection of 10 mg endotoxin, maternal intramuscular injection of 0.5 mg/kg betamethasone, both treatments combined or saline-treated controls. We quantified MMP-2 which is derived from connective tissue and MMP-9 which is predominantly derived from neutrophils in fetal lung fluid of lambs after maternal corticosteroid therapy and induction of chorioamnionitis and the combination of both therapies given at 109-111 days' gestational age with delivery 1, 5 or 15 days later.
  
  
  RESULTS
  Betamethasone, endotoxin and the combined treatments increased both surfactant pool size, lung gas volume and reduced alveolar wall thickness at 15 days. MMP-2 concentration was increased after betamethasone. MMP-9 concentration increased after endotoxin-induced chorioamnionitis but decreased by the combined treatments.
  
  
  CONCLUSIONS
  Lung maturation via different pathways may use different forms of collagenases for remodelling lung structure.
authors.affiliation: Department of Child Health, The Queen's University of Belfast, UK.
authors.forename: David G
authors.initials: DG
authors.lastname: Sweet
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Huggett
authors.forename: Jane A
authors.initials: JA
authors.lastname: Warner
authors.forename: Timothy J M
authors.initials: TJ
authors.lastname: Moss
authors.forename: Nico
authors.initials: N
authors.lastname: Kloosterboer
authors.forename: Henry L
authors.initials: HL
authors.lastname: Halliday
authors.forename: John P
authors.initials: JP
authors.lastname: Newnham
authors.forename: Suhas G
authors.initials: SG
authors.lastname: Kallapur
authors.forename: Alan H
authors.initials: AH
authors.lastname: Jobe
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
mesh_terms: D000650:Amnion / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001623:Betamethasone / Q000494:pharmacology*; D002821:Chorioamnionitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D004195:Disease Models, Animal; D004347:Drug Interactions; D004731:Endotoxins / Q000494:pharmacology; D004790:Enzyme Induction; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D005333:Fetus / Q000002:abnormalities / Q000187:drug effects* / Q000201:enzymology; D005938:Glucocorticoids / Q000494:pharmacology*; D007273:Injections, Intramuscular; D018811:Maternal Exposure; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D011247:Pregnancy; D011650:Pulmonary Alveoli / Q000002:abnormalities / Q000187:drug effects / Q000201:enzymology; D011663:Pulmonary Surfactants / Q000378:metabolism; D012756:Sheep
chemical_list: D004731:Endotoxins; D005938:Glucocorticoids; D011663:Pulmonary Surfactants; D001623:Betamethasone; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9