Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep

David Sweet, Matthew Huggett, Jane Warner, Timothy Moss, Nico Kloosterboer, Henry Halliday, John Newnham, Suhas Kallapur, Alan Jobe, Boris Kramer

Research output: Contribution to journalArticleResearchpeer-review

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. OBJECTIVES: 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. CONCLUSION: Lung maturation via different pathways may use different forms of collagenases for remodelling lung structure.
Original languageEnglish
Pages (from-to)79 - 86
Number of pages8
JournalNeonatology
Volume94
Issue number2
DOIs
Publication statusPublished - 2008
Externally publishedYes

Cite this

Sweet, D., Huggett, M., Warner, J., Moss, T., Kloosterboer, N., Halliday, H., ... Kramer, B. (2008). Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep. Neonatology, 94(2), 79 - 86. https://doi.org/10.1159/000115949
Sweet, David ; Huggett, Matthew ; Warner, Jane ; Moss, Timothy ; Kloosterboer, Nico ; Halliday, Henry ; Newnham, John ; Kallapur, Suhas ; Jobe, Alan ; Kramer, Boris. / Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep. In: Neonatology. 2008 ; Vol. 94, No. 2. pp. 79 - 86.
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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. OBJECTIVES: 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. CONCLUSION: Lung maturation via different pathways may use different forms of collagenases for remodelling lung structure.",
author = "David Sweet and Matthew Huggett and Jane Warner and Timothy Moss and Nico Kloosterboer and Henry Halliday and John Newnham and Suhas Kallapur and Alan Jobe and Boris Kramer",
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Sweet, D, Huggett, M, Warner, J, Moss, T, Kloosterboer, N, Halliday, H, Newnham, J, Kallapur, S, Jobe, A & Kramer, B 2008, 'Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep', Neonatology, vol. 94, no. 2, pp. 79 - 86. https://doi.org/10.1159/000115949

Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep. / Sweet, David; Huggett, Matthew; Warner, Jane; Moss, Timothy; Kloosterboer, Nico; Halliday, Henry; Newnham, John; Kallapur, Suhas; Jobe, Alan; Kramer, Boris.

In: Neonatology, Vol. 94, No. 2, 2008, p. 79 - 86.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Maternal betamethasone and chorioamnionitis induce different collagenases during lung maturation in fetal sheep

AU - Sweet, David

AU - Huggett, Matthew

AU - Warner, Jane

AU - Moss, Timothy

AU - Kloosterboer, Nico

AU - Halliday, Henry

AU - Newnham, John

AU - Kallapur, Suhas

AU - Jobe, Alan

AU - Kramer, Boris

PY - 2008

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N2 - 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. OBJECTIVES: 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. CONCLUSION: Lung maturation via different pathways may use different forms of collagenases for remodelling lung structure.

AB - 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. OBJECTIVES: 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. CONCLUSION: Lung maturation via different pathways may use different forms of collagenases for remodelling lung structure.

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