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 language | English (US) |
|---|---|
| Pages (from-to) | 2598-2606 |
| Number of pages | 9 |
| Journal | Journal of Clinical Investigation |
| Volume | 101 |
| Issue number | 11 |
| State | Published - Jun 1 1998 |
| Externally published | Yes |
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Keywords
- Cystic fibrosis
- Cystic fibrosis transmembrane conductance regulator
- Nuclear factor κB
- Pilin
- Pseudomonas aeruginosa
ASJC Scopus subject areas
- Medicine(all)
Cite this
Activation of NF-κB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells. / DiMango, E.; Ratner, A. J.; Bryan, R.; Tabibi, S.; Prince, A.
In: Journal of Clinical Investigation, Vol. 101, No. 11, 01.06.1998, p. 2598-2606.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Activation of NF-κB by adherent Pseudomonas aeruginosa in normal and cystic fibrosis respiratory epithelial cells
AU - DiMango, E.
AU - Ratner, A. J.
AU - Bryan, R.
AU - Tabibi, S.
AU - Prince, A.
PY - 1998/6/1
Y1 - 1998/6/1
N2 - 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.
AB - 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.
KW - Cystic fibrosis
KW - Cystic fibrosis transmembrane conductance regulator
KW - Nuclear factor κB
KW - Pilin
KW - Pseudomonas aeruginosa
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M3 - Article
VL - 101
SP - 2598
EP - 2606
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 11
ER -