Acute Pseudomonas challenge in cystic fibrosis mice causes prolonged nuclear factor-κB activation, cytokine secretion, and persistent lung inflammation - 17/08/11
![](/templates/common/images/mail.png)
![](/templates/common/images/entites/lowast.gif)
Cleveland, Ohio
Abstract |
Background |
Cystic fibrosis (CF) is characterized by an excessive and prolonged inflammatory response to Pseudomonas aeruginosa in the lung. There are high levels of cytokines and chemokines and an exaggerated PMN influx causing significant morbidity and mortality.
Objective |
To compare the kinetics of the inflammatory response with the kinetics of clearance of acute bacterial challenge in the lungs of CF and wild-type (WT) mice.
Methods |
We challenged CF knockout (KO) and WT mice intratracheally with P aeruginosa in suspension and evaluated bacteria counts, nuclear factor-κB (NF-κB), and inhibitor of NF-κB alpha protein (I-κB⍺) in lung tissue, cytokines, and PMN in bronchoalveolar lavage (BAL).
Results |
Both groups of mice cleared the infection with the same kinetics. CF-KO mice had more PMN in BAL than WT mice. CF-KO mice had high concentrations of proinflammatory cytokines in BAL on days 2 and 4, whereas cytokines in BAL from WT mice were only slightly elevated. CF-KO mice failed to regenerate I-κB⍺ once it was degraded, and consequently had prolonged and excessive activation of NF-κB for the entire 6-day duration of the study. In contrast, WT mice showed only slight NF-κB activation, which plateaued at day 4.
Conclusion |
These data suggest that NF-κB is dysregulated in CF lung infection and could be a good target for therapy. Prolonged responses to initial acute infections may contribute to the eventual establishment of chronic persistent inflammation.
Clinical implications |
Dysregulation of the I-κB/NF-κB pathway in cystic fibrosis leads to prolonged cytokine secretion and persistent inflammation in response to acute challenges and may be important in the development of chronic lung inflammation and infection.
Le texte complet de cet article est disponible en PDF.Key words : Cystic fibrosis, bronchoalveolar lavage, Pseudomonas aeruginosa, nuclear factor-κB, I-κB, lung, PMN
Abbreviations used : BAL, CF, CFTR, CFU, EMSA, I-κB, KO, MIP, NF-κB, WT
Plan
Supported by grants from the Cystic Fibrosis Foundation. Disclosure of potential conflict of interest: The authors have received grant support from the Cystic Fibrosis Foundation. |
Vol 117 - N° 5
P. 1163-1169 - mai 2006 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?