Maturational differences in lung NF-κB activation and their role in tolerance to hyperoxia

Neonatal rodents are more tolerant to hyperoxia than adults. We determined whether maturational differences in lung NF-kappaB activation could account for the differences. After hyperoxic exposure (O-2>95%), neonatal (<12 hours old) lung NF-kappa B binding was increased and reached a maximum between 8 and 16 hours, whereas in adults no changes were observed. Additionally, neonatal NF-kappa B/luciferase transgenic mice (incorporating 2 NF-kappa B consensus sequences driving luciferase gene expression) demonstrated enhanced in vivo NF-kappa B activation after hyperoxia in real time. In the lungs of neonates, there was a propensity toward NF-kappa B activation as evidenced by increased lung I-kappa B kinase protein levels, I-kappa B alpha phosphorylation, beta-transducin repeat-containing protein levels, and total I-kappa B alpha degradation. Increased lung p-JNK immunoreactive protein was observed only in the adult lung. Inhibition of pI-kappa B alpha by BAY 11-7085 resulted in decreased Bcl-2 protein levels in neonatal lung homogenates and decreased cell viability in lung primary cultures after hyperoxic exposure. Furthermore, neonatal p50-null mutant (p50(-/-)) mice showed increased lung DNA degradation and decreased survival in hyperoxia compared with WT mice. These data demonstrate that there are maturational differences in lung NF-kappa B activation and that enhanced NF-kappa B may serve to protect the neonatal lung from acute hyperoxic injury via inhibition of apoptosis.