Long-term pulmonary effects of intrauterine exposure to endotoxin following preterm birth in sheep.
Our aim was to determine whether fetal exposure to intraamniotic lipopolysaccharide (LPS) persistently alters the lungs following moderate preterm birth. Fetal sheep were exposed to LPS (1 mg/d) or saline from 0.75 to preterm birth at 0.90 of gestation. Eleven weeks after preterm birth, lung structure was unaltered. Interleukin (IL)-1β messenger RNA (mRNA) levels were elevated in lungs of LPS-exposed lambs (P < .05) but IL-1β protein levels were unaltered. Lung mRNA levels of IL-6, IL-8 and tumor necrosis factor α, and percentage of inflammatory cells were not different between groups. Surfactant protein (SP)-A and SP-C mRNA levels and SP-B tissue protein expression were higher in LPS-exposed lambs than controls (all P < .05); however, expression of SP-A and SP-C proteins was reduced. Prenatal LPS exposure causes a persistent increase in gene expression of proinflammatory mediators and surfactant proteins and a decrease in lung tissue SP-A and -C protein expression after preterm birth, which may affect lung immunity.
Department of Anatomy & Developmental Biology, Monash University, Clayton, Australia.
Anzari
A
Atik
Foula
F
Sozo
Sandra
S
Orgeig
Lakshmi
L
Suri
Takushi
T
Hanita
Richard
R
Harding
Robert
R
De Matteo
D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000235:genetics; D005260:Female; D015870:Gene Expression; D053583:Interleukin-1beta / Q000235:genetics; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008168:Lung / Q000737:chemistry / Q000276:immunology; D008171:Lung Diseases / Q000209:etiology / Q000378:metabolism / Q000662:veterinary*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D047928:Premature Birth / Q000662:veterinary*; D011297:Prenatal Exposure Delayed Effects / Q000662:veterinary; D037662:Pulmonary Surfactant-Associated Protein A / Q000032:analysis / Q000235:genetics; D037721:Pulmonary Surfactant-Associated Protein C / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012756:Sheep; D012757:Sheep Diseases / Q000209:etiology*
D016207:Cytokines; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D037662:Pulmonary Surfactant-Associated Protein A; D037721:Pulmonary Surfactant-Associated Protein C; D012333:RNA, Messenger