Effects of antenatal lipopolysaccharide and postnatal hyperoxia on airway reactivity and remodeling in a neonatal mouse model

Arij Faksh, Rodney Jr. Britt, Elizabeth R. Vogel, Ine Kuipers, Michael A. Thompson, Gary C Sieck, Christina M Pabelick, Richard J. Martin, Y.s. Prakash

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 d 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. Upregulation 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.

Original languageEnglish (US)
Pages (from-to)391-400
Number of pages10
JournalPediatric Research
Volume79
Issue number3
DOIs
StatePublished - Mar 1 2016

Fingerprint

Airway Remodeling
Hyperoxia
Lipopolysaccharides
Inflammation
Smooth Muscle
Dissection
Lasers
Mothers
Connective Tissue Growth Factor
Respiratory Sounds
Premature Birth
Transforming Growth Factors
Mechanics
Compliance
Histology
Up-Regulation
Collagen
Asthma
Air
Parturition

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Effects of antenatal lipopolysaccharide and postnatal hyperoxia on airway reactivity and remodeling in a neonatal mouse model. / Faksh, Arij; Britt, Rodney Jr.; Vogel, Elizabeth R.; Kuipers, Ine; Thompson, Michael A.; Sieck, Gary C; Pabelick, Christina M; Martin, Richard J.; Prakash, Y.s.

In: Pediatric Research, Vol. 79, No. 3, 01.03.2016, p. 391-400.

Research output: Contribution to journalArticle

Faksh, Arij ; Britt, Rodney Jr. ; Vogel, Elizabeth R. ; Kuipers, Ine ; Thompson, Michael A. ; Sieck, Gary C ; Pabelick, Christina M ; Martin, Richard J. ; Prakash, Y.s. / Effects of antenatal lipopolysaccharide and postnatal hyperoxia on airway reactivity and remodeling in a neonatal mouse model. In: Pediatric Research. 2016 ; Vol. 79, No. 3. pp. 391-400.
@article{d3ebacc04a4841a09a6694a3d6289ce3,
title = "Effects of antenatal lipopolysaccharide and postnatal hyperoxia on airway reactivity and remodeling in a neonatal mouse model",
abstract = "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 d 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. Upregulation 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.",
author = "Arij Faksh and Britt, {Rodney Jr.} and Vogel, {Elizabeth R.} and Ine Kuipers and Thompson, {Michael A.} and Sieck, {Gary C} and Pabelick, {Christina M} and Martin, {Richard J.} and Y.s. Prakash",
year = "2016",
month = "3",
day = "1",
doi = "10.1038/pr.2015.232",
language = "English (US)",
volume = "79",
pages = "391--400",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "3",

}

TY - JOUR

T1 - Effects of antenatal lipopolysaccharide and postnatal hyperoxia on airway reactivity and remodeling in a neonatal mouse model

AU - Faksh, Arij

AU - Britt, Rodney Jr.

AU - Vogel, Elizabeth R.

AU - Kuipers, Ine

AU - Thompson, Michael A.

AU - Sieck, Gary C

AU - Pabelick, Christina M

AU - Martin, Richard J.

AU - Prakash, Y.s.

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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 d 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. Upregulation 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.

AB - 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 d 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. Upregulation 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.

UR - http://www.scopus.com/inward/record.url?scp=84962677896&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962677896&partnerID=8YFLogxK

U2 - 10.1038/pr.2015.232

DO - 10.1038/pr.2015.232

M3 - Article

C2 - 26539665

AN - SCOPUS:84962677896

VL - 79

SP - 391

EP - 400

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 3

ER -