期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 117, 期 5, 页码 1163-1169出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2006.01.052
关键词
cystic fibrosis; bronchoalveolar lavage; Pseudomonas aeruginosa; nuclear factor-kappa B; 1-kappa B; lung; PMN
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-kappa B (NF-kappa B), and inhibitor of NF-kappa B alpha protein (I-kappa B alpha) 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-kappa B alpha once it was degraded, and consequently had prolonged and excessive activation of NF-kappa B for the entire 6-day duration or the study. In contrast, WT mice showed only slight NF-kappa B activation, which plateaued at day 4. Conclusion: These data suggest that NF-kappa B is dysregulated in CIF 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-kappa B/NF-kappa B 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.
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