| First Author | Michaelis KA | Year | 2014 |
| Journal | Am J Respir Cell Mol Biol | Volume | 50 |
| Issue | 2 | Pages | 429-38 |
| PubMed ID | 24066808 | Mgi Jnum | J:231864 |
| Mgi Id | MGI:5775267 | Doi | 10.1165/rcmb.2013-0303OC |
| Citation | Michaelis KA, et al. (2014) IkappaBbeta-mediated NF-kappaB activation confers protection against hyperoxic lung injury. Am J Respir Cell Mol Biol 50(2):429-38 |
| abstractText | Supplemental oxygen is frequently used in an attempt to improve oxygen delivery; however, prolonged exposure results in damage to the pulmonary endothelium and epithelium. Although NF-kappaB has been identified as a redox-responsive transcription factor, whether NF-kappaB activation exacerbates or attenuates hyperoxic lung injury is unclear. We determined that sustained NF-kappaB activity mediated by IkappaBbeta attenuates lung injury and prevents mortality in adult mice exposed to greater than 95% O2. Adult wild-type mice demonstrated evidence of alveolar protein leak and 100% mortality by 6 days of hyperoxic exposure, and showed NF-kappaB nuclear translocation that terminated after 48 hours. Furthermore, these mice showed increased expression of NF-kappaB-regulated proinflammatory and proapoptotic cytokines. In contrast, mice overexpressing the NF-kappaB inhibitory protein, IkappaBbeta (AKBI), demonstrated significant resistance to hyperoxic lung injury, with 50% surviving through 8 days of exposure. This was associated with NF-kappaB nuclear translocation that persisted through 96 hours of exposure. Although induction of NF-kappaB-regulated proinflammatory cytokines was not different between wild-type and AKBI mice, significant up-regulation of antiapoptotic proteins (BCL-2, BCL-XL) was found exclusively in AKBI mice. We conclude that sustained NF-kappaB activity mediated by IkappaBbeta protects against hyperoxic lung injury through increased expression of antiapoptotic genes. |
