Chien-Ling Su1, Hsiu-Chu Chou2, Liang-Ti Huang3, Tsu-Fu Yeh4, Chung-Ming Chen5. 1. School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan. 2. Department of Anatomy, College of Medicine, Taipei Medical University, Taipei, Taiwan. 3. Department of Pediatrics, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan. 4. Maternal Child Health Research Center, College of Medicine, Taipei Medical University, Taipei, Taiwan. 5. 1] Maternal Child Health Research Center, College of Medicine, Taipei Medical University, Taipei, Taiwan [2] Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan [3] Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Abstract
BACKGROUND: Receptors for advanced glycation end products (RAGE) have been implicated in fibrotic processes. We hypothesized that lung fibrosis induced by maternal lipopolysaccharide (LPS)-mediated inflammation and neonatal hyperoxia involves RAGE in newborn rats. METHODS: Pregnant Sprague-Dawley rats received intraperitoneal injections of LPS or normal saline (NS) on 20 and 21 d of gestation. The pups were reared in room air (RA) or an O2-enrich atmosphere (O2), creating the four study groups, NS + RA, NS + O2, LPS + RA, and LPS + O2. The O2 treatment was >95% O2 for 7 d, followed by 60% O2 for 14 d. RESULTS: Rat pups born to LPS-injected dams exhibited significantly higher lung interferon-γ and interleukin-1β (IL-1β) on postnatal day 7 than the pups born to NS-injected dams. Rat pups reared in hyperoxia expressed higher lung IL-10 on postnatal day 7, compared with the RA-reared pups. The LPS + O2 group had significantly higher total collagen and transforming growth factor-β1 on postnatal days 7 and 21 than the NS+RA group. RAGE mRNA and sRAGE protein expression were significantly lower in the LPS + O2 group on postnatal day 7 than the NS+RA group. CONCLUSION: RAGE may be involved in the pathogenesis of lung fibrosis induced by maternal systemic inflammation and postnatal hyperoxia in rat neonates.
BACKGROUND:Receptors for advanced glycation end products (RAGE) have been implicated in fibrotic processes. We hypothesized that lung fibrosis induced by maternal lipopolysaccharide (LPS)-mediated inflammation and neonatal hyperoxia involves RAGE in newborn rats. METHODS: Pregnant Sprague-Dawley rats received intraperitoneal injections of LPS or normal saline (NS) on 20 and 21 d of gestation. The pups were reared in room air (RA) or an O2-enrich atmosphere (O2), creating the four study groups, NS + RA, NS + O2, LPS + RA, and LPS + O2. The O2 treatment was >95% O2 for 7 d, followed by 60% O2 for 14 d. RESULTS:Rat pups born to LPS-injected dams exhibited significantly higher lung interferon-γ and interleukin-1β (IL-1β) on postnatal day 7 than the pups born to NS-injected dams. Rat pups reared in hyperoxia expressed higher lung IL-10 on postnatal day 7, compared with the RA-reared pups. The LPS + O2 group had significantly higher total collagen and transforming growth factor-β1 on postnatal days 7 and 21 than the NS+RA group. RAGE mRNA and sRAGE protein expression were significantly lower in the LPS + O2 group on postnatal day 7 than the NS+RA group. CONCLUSION:RAGE may be involved in the pathogenesis of lung fibrosis induced by maternal systemic inflammation and postnatal hyperoxia in rat neonates.