Targeted immunomodulation of the NF-κB pathway in airway epithelium impacts host defense against Pseudomonas aeruginosa

Ruxana T. Sadikot, Heng Zeng, Myungsoo Joo, M. Brett Everhart, Taylor P. Sherrill, Bo Li, Dong Sheng Cheng, Fiona E. Yull, John W. Christman, Timothy S. Blackwell

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

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-κB 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-κB activity in airway epithelium by intratracheal delivery of adenoviral vectors expressing RelA (AdRelA) or a dominant inhibitor of NF-κB before P. aeruginosa infection. Bacterial clearance was enhanced by up-regulation of NF-κB activity following AdRelA administration and was impaired by treatment with a dominant inhibitor of NF-κB. The TNF-α concentration in lung lavage was increased by AdRelA treatment and beneficial effects of NF-κB up-regulation were abrogated in TNF-α-deficient mice. In contrast, NF-κB inhibition reduced MIP-2 expression and neutrophil influx following P. aeruginosa infection. Therefore, inflammatory signaling through the NF-κB pathway in airway epithelial cells critically regulates the innate immune response to P. aeruginosa.

Original languageEnglish (US)
Pages (from-to)4923-4930
Number of pages8
JournalJournal of Immunology
Volume176
Issue number8
DOIs
StatePublished - Apr 15 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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