| First Author | Sadikot RT | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 8 | Pages | 4923-30 |
| PubMed ID | 16585588 | Mgi Jnum | J:131185 |
| Mgi Id | MGI:3773121 | Doi | 10.4049/jimmunol.176.8.4923 |
| Citation | Sadikot RT, et al. (2006) Targeted immunomodulation of the NF-kappaB pathway in airway epithelium impacts host defense against Pseudomonas aeruginosa. J Immunol 176(8):4923-30 |
| abstractText | We investigated the impact of inflammatory signaling in airway epithelial cells on host defense against Pseudomonas aeruginosa, a major cause of nosocomial pneumonia. In mice, airway instillation of P. aeruginosa resulted in NF-kappaB activation in the lungs that was primarily localized to the bronchial epithelium at 4 h, but was present in a variety of cell types by 24 h. We modulated NF-kappaB activity in airway epithelium by intratracheal delivery of adenoviral vectors expressing RelA (AdRelA) or a dominant inhibitor of NF-kappaB before P. aeruginosa infection. Bacterial clearance was enhanced by up-regulation of NF-kappaB activity following AdRelA administration and was impaired by treatment with a dominant inhibitor of NF-kappaB. The TNF-alpha concentration in lung lavage was increased by AdRelA treatment and beneficial effects of NF-kappaB up-regulation were abrogated in TNF-alpha-deficient mice. In contrast, NF-kappaB inhibition reduced MIP-2 expression and neutrophil influx following P. aeruginosa infection. Therefore, inflammatory signaling through the NF-kappaB pathway in airway epithelial cells critically regulates the innate immune response to P. aeruginosa. |
