Activation of NF-κB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells

E. DiMango, A. J. Ratner, R. Bryan, S. Tabibi, A. Prince

Research output: Contribution to journalArticle

263 Scopus citations

Abstract

PMN-dominated airway inflammation is a major component of cystic fibrosis (CF) lung disease. Epithelial cells respond to organisms such as Pseudomonas aeruginosa, the major pathogen in CF, by expressing the leukocyte chemokine IL-8. Experiments were performed using several different types of respiratory epithelial cells that demonstrate that ligation of ceramide- associated receptors on epithelial surfaces by P. aeruginosa pili is a major stimulus for the translocation of transcription factor nuclear factor (NF)- κB and initiation of IL-8 expression by epithelial cells. Using electrophoretic mobility shift assays and Western hybridizations, nuclear NF- κB was found shortly after epithelial cells were stimulated by either whole organisms, isolated pili, or antibody to the pilin receptor asialoGM1. IB3 cells, which express mutations in cystic fibrosis transmembrane conductance regulator (CFTR) (ΔF508/W1282X), were noted to have significantly greater amounts of endogenous nuclear NF-κB, but not the transcription factor C/EBP, than CF cells corrected by episomal copies of normal CFTR (C-38) or IB3 cells grown at a permissive temperature (25°C). Activation of NF-κB and subsequent IL-8 expression in epithelial cells can result from activation of at least two pathways: an exogenous signaling cascade that is activated by ligation of ceramide-associated adhesins such as P. aeruginosa pilin, or endogenous stimulation, suggested to be a consequence of cell stress caused by the accumulation of mutant CFTR in the endoplasmic reticulum.

Original languageEnglish (US)
Pages (from-to)2598-2606
Number of pages9
JournalJournal of Clinical Investigation
Volume101
Issue number11
StatePublished - Jun 1 1998

Keywords

  • Cystic fibrosis
  • Cystic fibrosis transmembrane conductance regulator
  • Nuclear factor κB
  • Pilin
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Medicine(all)

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