description): Premature newborns are at high risk of developing bronchopulmonary dysplasia (BPD). This chronic lung disease has been traditionally viewed as the result of postnatal insults, such as hyperoxia or barotrauma. Recent evidence, however, indicates that the injury leading to BPD may begin before birth. Increased concentration of the proinflammatory cytokine interleukin-l (IL-1) in amniotic fluid has been shown to be a risk factor for the development of BPD in the newborn infant. Other studies indicate that IL-la in the amniotic fluid causes early lung maturation in animal models. The central hypothesis is that antenatal exposure of the lung to inflammatory stimuli such as IL-1 modifies pre- and postnatal development of the lung and the responses of the lung to postnatal adversities. The specific objective is to study how prenatal overexpression of IL-l alpha in the lung modifies lung development and the response of the lung to postnatal hyperoxic injury.
The aims of the present proposal are:
Aim 1 : To generate a transgenic mouse in which IL-l alpha is expressed in a lung-specific fashion in an externally regulatable manner and to study how activation of IL-l alpha expression in the lung during the saccular and alveolar periods of lung development affects the pulmonary phenotype of this transgenic mouse.
Aim 2 : To study how antenatal overexpression of IL-1 alpha in the lung affects the response of the lung to hyperoxic exposure after birth.
| Bry, Kristina; Whitsett, Jeffrey A; Lappalainen, Urpo (2007) IL-1beta disrupts postnatal lung morphogenesis in the mouse. Am J Respir Cell Mol Biol 36:32-42 |
| Lappalainen, Urpo; Whitsett, Jeffrey A; Wert, Susan E et al. (2005) Interleukin-1beta causes pulmonary inflammation, emphysema, and airway remodeling in the adult murine lung. Am J Respir Cell Mol Biol 32:311-8 |
