NF-κB induces lung maturation during mouse lung morphogenesis

Lung maturation is hallmarked by the appearance of surfactant-producing alveoli during transition from the saccular to alveolar stage of lung development. Inflammation can disrupt this process and accelerate lung maturity following intrauterine amniotic infection (chorioamnionitis). Nuclear factor kappa B (NF-kappa B) is a transcription factor central to multiple inflammatory and developmental pathways, including dorsal-ventral patterning in fruit flies, limb and mammary and submandibular gland development in mice, and branching morphogenesis in chick lungs. Given its shared role in inflammation and developmental signaling, we hypothesized that overexpression of NF-kappa B targeted to the lung epithelium would exert maturational effects on alveolar development. We generated transgenic mice with lung-specific overexpression of the Re1A subunit of NF-kappa B using a surfactant protein C promoter construct. Our results showed that Re1A overexpression in the lung yields increased alveolar type I and type 11 cells. These findings are consistent with a model whereby NF-kappa B may induce maturation of lung development through decreased apoptosis of epithelial cells.