科研之友
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摘要
Chorioamnionitis alters lung development, resulting in a paradoxical decrease in the incidence of respiratory distress syndrome but an increase in the incidence of bronchopulmonary dysplasia ( BPD). The mechanism( s) underlying this disparity in the pulmonary outcomes is not known. We hypothesized that specific alterations in alveolar epithelial- mesenchymal interactions might explain this apparent disparity in the pulmonary outcome following chorioamnionitis. We determined the effects of lipopolysaccharide ( LPS) on parathyroid hormone- related protein ( PTHrP)- driven epithelial- mesenchymal interactions that are essential for normal lung development and homeostasis. Lung explants from embryonic day 19.5 Sprague- Dawley rat fetuses were treated with LPS with or without a PTHrP pathway agonist, prostaglandin J(2) ( PGJ(2)). LPS treatment affected the production of proinflammatory cytokines and the expression of the key markers of the epithelial-mesenchymal paracrine interactions in a time- dependent manner. At 6 h, there was a significant increase in the expression of PTHrP and the other key markers of alveolar homeostasis without any significant effect on alpha-smooth muscle actin (alpha SMA). In contrast, at 72 h, there was a significant decrease in the expression of PTHrP and the other key markers of alveolar homeostasis accompanied by a significant increase in alpha SMA expression. The cytokine and molecular changes at 72 h were completely prevented by the concomitant treatment with PGJ2. We speculate that these data provide a likely mechanism for the acute stimulation of lung differentiation, accompanied paradoxically by BPD following chorioamnionitis, and suggest that by specifically targeting PTHrP signaling, the inflammation- induced molecular injury that is known to result in BPD can be prevented.
- 出版日期2007-7
