Abstract

Fetal sheep will be exposed to intraamniotic endotoxin and the minimal effective dose determined as well as the effects of prolonged low dose exposure. Subsequently, the route of the effects of endotoxin will be evaluated by targeting the stimulus to the amniotic cavity, the systemic circulation, the GI tract, or the lungs. All lambs exposed in utero will be delivered preterm and evaluated for indicators of amniotic space inflammation, lung function, and lung biochemical indicators of maturation. Candidate mediators, identified by evaluating the fetal responses to endotoxin, will be tested for their ability to induce fetal responses and lung maturation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL065397-03
Application #
6527359
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Berberich, Mary Anne
Project Start
2000-09-01
Project End
2004-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
3
Fiscal Year
2002
Total Cost
$323,955
Indirect Cost

  Institution

Name
Cincinnati Children's Hospital Medical Center
Department
Type
DUNS #
071284913
City
Cincinnati
State
OH
Country
United States
Zip Code
45229

  Publications

Kunzmann, Steffen; Collins, Jennifer J P; Yang, Yang et al. (2011) Antenatal inflammation reduces expression of caveolin-1 and influences multiple signaling pathways in preterm fetal lungs. Am J Respir Cell Mol Biol 45:969-76
Seehase, Matthias; Gantert, Markus; Ladenburger, Andreas et al. (2011) Myocardial response in preterm fetal sheep exposed to systemic endotoxinaemia. Pediatr Res 70:242-6
Jobe, Alan H (2011) The new bronchopulmonary dysplasia. Curr Opin Pediatr 23:167-72
Shah, Tushar A; Hillman, Noah H; Nitsos, Ilias et al. (2010) Pulmonary and systemic expression of monocyte chemotactic proteins in preterm sheep fetuses exposed to lipopolysaccharide-induced chorioamnionitis. Pediatr Res 68:210-5
Kunzmann, Steffen; Glogger, Kerstin; Been, Jasper V et al. (2010) Thymic changes after chorioamnionitis induced by intraamniotic lipopolysaccharide in fetal sheep. Am J Obstet Gynecol 202:476.e1-9
Knox, Christine L; Dando, Samantha J; Nitsos, Ilias et al. (2010) The severity of chorioamnionitis in pregnant sheep is associated with in vivo variation of the surface-exposed multiple-banded antigen/gene of Ureaplasma parvum. Biol Reprod 83:415-26
Ladenburger, Andreas; Seehase, Matthias; Kramer, Boris W et al. (2010) Glucocorticoids potentiate IL-6-induced SP-B expression in H441 cells by enhancing the JAK-STAT signaling pathway. Am J Physiol Lung Cell Mol Physiol 299:L578-84
Kramer, Boris W; Kallapur, Suhas G; Moss, Timothy J M et al. (2010) Modulation of fetal inflammatory response on exposure to lipopolysaccharide by chorioamnion, lung, or gut in sheep. Am J Obstet Gynecol 202:77.e1-9
Kramer, Boris W; Kallapur, Suhas; Newnham, John et al. (2009) Prenatal inflammation and lung development. Semin Fetal Neonatal Med 14:2-7
Kramer, Boris W; Kallapur, Suhas G; Moss, Timothy J et al. (2009) Intra-amniotic LPS modulation of TLR signaling in lung and blood monocytes of fetal sheep. Innate Immun 15:101-7

Showing the most recent 10 out of 54 publications