PMID- 24788984
OWN - NLM
STAT- MEDLINE
DCOM- 20150122
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 4
DP  - 2014
TI  - Ventilation-induced increases in EGFR ligand mRNA are not altered by 
      intra-amniotic LPS or ureaplasma in preterm lambs.
PG  - e96087
LID - 10.1371/journal.pone.0096087 [doi]
LID - e96087
AB  - Chorioamnionitis and mechanical ventilation are associated with bronchopulmonary 
      dysplasia (BPD) in preterm infants. Mechanical ventilation at birth activates 
      both inflammatory and acute phase responses. These responses can be partially 
      modulated by previous exposure to intra-amniotic (IA) LPS or Ureaplasma parvum 
      (UP). Epidermal growth factor receptor (EGFR) ligands participate in lung 
      development, and angiotensin converting enzyme (ACE) 1 and ACE2 contribute to 
      lung inflammation. We asked whether brief mechanical ventilation at birth altered 
      EGFR and ACE pathways and if antenatal exposure to IA LPS or UP could modulate 
      these effects. Ewes were exposed to IA injections of UP, LPS or saline multiple 
      days prior to preterm delivery at 85% gestation. Lambs were either immediately 
      euthanized or mechanically ventilated for 2 to 3 hr. IA UP and LPS cause modest 
      changes in the EGFR ligands amphiregulin (AREG), epiregulin (EREG), heparin 
      binding epidermal growth factor (HB-EGF), and betacellulin (BTC) mRNA expression. 
      Mechanical ventilation greatly increased mRNA expression of AREG, EREG, and 
      HB-EGF, with no additional increases resulting from IA LPS or UP. With 
      ventilation AREG and EREG mRNA localized to cells in terminal airspace. EGFR mRNA 
      also increased with mechanical ventilation. IA UP and LPS decreased ACE1 mRNA and 
      increased ACE2 mRNA, resulting in a 4 fold change in the ACE1/ACE2 ratio. 
      Mechanical ventilation with large tidal volumes increased both ACE1 and ACE2 
      expression. The alterations seen in ACE with IA exposures and EGFR pathways with 
      mechanical ventilation may contribute to the development of BPD in preterm 
      infants.
FAU - Hillman, Noah H
AU  - Hillman NH
AD  - Division of Neonatology, Saint Louis University, Saint Louis, Missouri, United 
      States of America; Division of Pulmonary Biology, Cincinnati Children's Hospital 
      Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of 
      America.
FAU - Gisslen, Tate
AU  - Gisslen T
AD  - Division of Neonatology, Saint Louis University, Saint Louis, Missouri, United 
      States of America.
FAU - Polglase, Graeme R
AU  - Polglase GR
AD  - School of Women and Infants' Health, University of Western Australia Perth, WA, 
      Australia; The Ritchie Centre, Monash Institute of Medical Research, Monash 
      University, Melbourne, VIC, Australia.
FAU - Kallapur, Suhas G
AU  - Kallapur SG
AD  - Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, 
      University of Cincinnati, Cincinnati, Ohio, United States of America; School of 
      Women and Infants' Health, University of Western Australia Perth, WA, Australia.
FAU - Jobe, Alan H
AU  - Jobe AH
AD  - Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, 
      University of Cincinnati, Cincinnati, Ohio, United States of America; School of 
      Women and Infants' Health, University of Western Australia Perth, WA, Australia.
LA  - eng
GR  - R01-HD072842/HD/NICHD NIH HHS/United States
GR  - R01 HD072842/HD/NICHD NIH HHS/United States
GR  - R01 HD057869/HD/NICHD NIH HHS/United States
GR  - R01-HD12714/HD/NICHD NIH HHS/United States
GR  - K08 HL097085/HL/NHLBI NIH HHS/United States
GR  - R01 HD012714/HD/NICHD NIH HHS/United States
GR  - K08-HL097085/HL/NHLBI NIH HHS/United States
GR  - R01-HD57869/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140430
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Ligands)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
SB  - IM
MH  - Amnion/*metabolism
MH  - Animals
MH  - *Animals, Newborn
MH  - ErbB Receptors/*metabolism
MH  - Female
MH  - In Situ Hybridization
MH  - Ligands
MH  - Lipopolysaccharides/*metabolism
MH  - *Obstetric Labor, Premature
MH  - Peptidyl-Dipeptidase A/genetics
MH  - Polymerase Chain Reaction
MH  - Pregnancy
MH  - RNA, Messenger/*metabolism
MH  - *Respiration, Artificial
MH  - Sheep
MH  - Ureaplasma/*isolation & purification
PMC - PMC4005755
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/05/03 06:00
MHDA- 2015/01/23 06:00
PMCR- 2014/04/30
CRDT- 2014/05/03 06:00
PHST- 2013/11/15 00:00 [received]
PHST- 2014/04/02 00:00 [accepted]
PHST- 2014/05/03 06:00 [entrez]
PHST- 2014/05/03 06:00 [pubmed]
PHST- 2015/01/23 06:00 [medline]
PHST- 2014/04/30 00:00 [pmc-release]
AID - PONE-D-13-48144 [pii]
AID - 10.1371/journal.pone.0096087 [doi]
PST - epublish
SO  - PLoS One. 2014 Apr 30;9(4):e96087. doi: 10.1371/journal.pone.0096087. eCollection 
      2014.