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Maturational differences in lung NF-κB activation and their role in tolerance to hyperoxia
Guang Yang, … , Yi-Hao Weng, Phyllis A. Dennery
Guang Yang, … , Yi-Hao Weng, Phyllis A. Dennery
Published September 1, 2004
Citation Information: J Clin Invest. 2004;114(5):669-678. https://doi.org/10.1172/JCI19300.
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Article Inflammation

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

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Abstract

Neonatal rodents are more tolerant to hyperoxia than adults. We determined whether maturational differences in lung NF-κB activation could account for the differences. After hyperoxic exposure (O2 > 95%), neonatal (<12 hours old) lung NF-κB binding was increased and reached a maximum between 8 and 16 hours, whereas in adults no changes were observed. Additionally, neonatal NF-κB/luciferase transgenic mice (incorporating 2 NF-κB consensus sequences driving luciferase gene expression) demonstrated enhanced in vivo NF-κB activation after hyperoxia in real time. In the lungs of neonates, there was a propensity toward NF-κB activation as evidenced by increased lung I-κB kinase protein levels, I-κBα phosphorylation, β-transducin repeat–containing protein levels, and total I-κBα degradation. Increased lung p-JNK immunoreactive protein was observed only in the adult lung. Inhibition of pI-κBα 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-κB activation and that enhanced NF-κB may serve to protect the neonatal lung from acute hyperoxic injury via inhibition of apoptosis.

Authors

Guang Yang, Aida Abate, Adia G. George, Yi-Hao Weng, Phyllis A. Dennery

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Figure 7

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Effect of inhibition of I-κΒα phosphorylation on primary lung cells expo...
Effect of inhibition of I-κΒα phosphorylation on primary lung cells exposed to hyperoxia. (A) Visualization of NF-κB activation in primary lung cells cultured from NF-κB/luc Tg mice. (B) Effect of inhibition of I-κΒα phosphorylation on NF-κB activation. Cells were incubated with 1 mM BAY 11-7085 or BAY 11-7082 and then exposed to 24 hours of hyperoxia. Controls were incubated with 0.1% ethanol, the vehicle for BAY. Note the decreased light intensity after BAY treatment. (C) Cell viability was evaluated using trypan blue exclusion. The number of surviving cells in each group was assessed after 24 hours of hyperoxic exposure.
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