Cargando…
Effects of Antenatal Lipopolysaccharide and Postnatal Hyperoxia on Airway Reactivity and Remodeling in a Neonatal Mouse Model
BACKGROUND: Antenatal inflammation and preterm birth are associated with the development of airway diseases such as wheezing and asthma. Utilizing a newborn mouse model, we assessed the effects of maternal inflammation and postnatal hyperoxia on the neonatal airway. METHODS: Pregnant C57/Bl6 dams we...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821779/ https://www.ncbi.nlm.nih.gov/pubmed/26539665 http://dx.doi.org/10.1038/pr.2015.232 |
_version_ | 1782425635139878912 |
---|---|
author | Faksh, Arij Britt, Rodney D. Vogel, Elizabeth R. Kuipers, Ine Thompson, Michael A. Sieck, Gary C. Pabelick, Christina M. Martin, Richard J. Prakash, YS |
author_facet | Faksh, Arij Britt, Rodney D. Vogel, Elizabeth R. Kuipers, Ine Thompson, Michael A. Sieck, Gary C. Pabelick, Christina M. Martin, Richard J. Prakash, YS |
author_sort | Faksh, Arij |
collection | PubMed |
description | BACKGROUND: Antenatal inflammation and preterm birth are associated with the development of airway diseases such as wheezing and asthma. Utilizing a newborn mouse model, we assessed the effects of maternal inflammation and postnatal hyperoxia on the neonatal airway. METHODS: Pregnant C57/Bl6 dams were injected with lipopolysaccharide (LPS) or saline on embryonic day 16. Offspring were placed in room air or hyperoxia (50% O(2)) for 7 days and then returned to normoxia. Airway mechanics, histology, and laser capture micro-dissection (LCM) were performed. RESULTS: At postnatal day 21, maternal LPS- and 50% O(2)-exposed pups exhibited increased resistance and decreased compliance compared to 21% O(2) pups; however their effects were not synergistic. LPS and hyperoxia each increased the thickness of airway smooth muscle (ASM), but not the airway epithelial layer. Structural changes were largely limited to the conducting airways. Up-regulation of inflammatory markers in the lung was observed at birth. LCM revealed increased collagen-3, transforming growth factor β, and connective tissue growth factor expression with LPS and hyperoxia within the ASM layer. CONCLUSION: These novel studies provide functional, structural and molecular evidence that antenatal inflammation is detrimental to the developing airway. Exposure to moderate hyperoxia does not exacerbate LPS effects on the airway. |
format | Online Article Text |
id | pubmed-4821779 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-48217792016-05-18 Effects of Antenatal Lipopolysaccharide and Postnatal Hyperoxia on Airway Reactivity and Remodeling in a Neonatal Mouse Model Faksh, Arij Britt, Rodney D. Vogel, Elizabeth R. Kuipers, Ine Thompson, Michael A. Sieck, Gary C. Pabelick, Christina M. Martin, Richard J. Prakash, YS Pediatr Res Article BACKGROUND: Antenatal inflammation and preterm birth are associated with the development of airway diseases such as wheezing and asthma. Utilizing a newborn mouse model, we assessed the effects of maternal inflammation and postnatal hyperoxia on the neonatal airway. METHODS: Pregnant C57/Bl6 dams were injected with lipopolysaccharide (LPS) or saline on embryonic day 16. Offspring were placed in room air or hyperoxia (50% O(2)) for 7 days and then returned to normoxia. Airway mechanics, histology, and laser capture micro-dissection (LCM) were performed. RESULTS: At postnatal day 21, maternal LPS- and 50% O(2)-exposed pups exhibited increased resistance and decreased compliance compared to 21% O(2) pups; however their effects were not synergistic. LPS and hyperoxia each increased the thickness of airway smooth muscle (ASM), but not the airway epithelial layer. Structural changes were largely limited to the conducting airways. Up-regulation of inflammatory markers in the lung was observed at birth. LCM revealed increased collagen-3, transforming growth factor β, and connective tissue growth factor expression with LPS and hyperoxia within the ASM layer. CONCLUSION: These novel studies provide functional, structural and molecular evidence that antenatal inflammation is detrimental to the developing airway. Exposure to moderate hyperoxia does not exacerbate LPS effects on the airway. 2015-11-05 2016-03 /pmc/articles/PMC4821779/ /pubmed/26539665 http://dx.doi.org/10.1038/pr.2015.232 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Faksh, Arij Britt, Rodney D. Vogel, Elizabeth R. Kuipers, Ine Thompson, Michael A. Sieck, Gary C. Pabelick, Christina M. Martin, Richard J. Prakash, YS Effects of Antenatal Lipopolysaccharide and Postnatal Hyperoxia on Airway Reactivity and Remodeling in a Neonatal Mouse Model |
title | Effects of Antenatal Lipopolysaccharide and Postnatal Hyperoxia on Airway Reactivity and Remodeling in a Neonatal Mouse Model |
title_full | Effects of Antenatal Lipopolysaccharide and Postnatal Hyperoxia on Airway Reactivity and Remodeling in a Neonatal Mouse Model |
title_fullStr | Effects of Antenatal Lipopolysaccharide and Postnatal Hyperoxia on Airway Reactivity and Remodeling in a Neonatal Mouse Model |
title_full_unstemmed | Effects of Antenatal Lipopolysaccharide and Postnatal Hyperoxia on Airway Reactivity and Remodeling in a Neonatal Mouse Model |
title_short | Effects of Antenatal Lipopolysaccharide and Postnatal Hyperoxia on Airway Reactivity and Remodeling in a Neonatal Mouse Model |
title_sort | effects of antenatal lipopolysaccharide and postnatal hyperoxia on airway reactivity and remodeling in a neonatal mouse model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4821779/ https://www.ncbi.nlm.nih.gov/pubmed/26539665 http://dx.doi.org/10.1038/pr.2015.232 |
work_keys_str_mv | AT faksharij effectsofantenatallipopolysaccharideandpostnatalhyperoxiaonairwayreactivityandremodelinginaneonatalmousemodel AT brittrodneyd effectsofantenatallipopolysaccharideandpostnatalhyperoxiaonairwayreactivityandremodelinginaneonatalmousemodel AT vogelelizabethr effectsofantenatallipopolysaccharideandpostnatalhyperoxiaonairwayreactivityandremodelinginaneonatalmousemodel AT kuipersine effectsofantenatallipopolysaccharideandpostnatalhyperoxiaonairwayreactivityandremodelinginaneonatalmousemodel AT thompsonmichaela effectsofantenatallipopolysaccharideandpostnatalhyperoxiaonairwayreactivityandremodelinginaneonatalmousemodel AT sieckgaryc effectsofantenatallipopolysaccharideandpostnatalhyperoxiaonairwayreactivityandremodelinginaneonatalmousemodel AT pabelickchristinam effectsofantenatallipopolysaccharideandpostnatalhyperoxiaonairwayreactivityandremodelinginaneonatalmousemodel AT martinrichardj effectsofantenatallipopolysaccharideandpostnatalhyperoxiaonairwayreactivityandremodelinginaneonatalmousemodel AT prakashys effectsofantenatallipopolysaccharideandpostnatalhyperoxiaonairwayreactivityandremodelinginaneonatalmousemodel |