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MPB-07 Reduces the Inflammatory Response to Pseudomonas aeruginosa in CF Bronchial Cells
- Source :
- American Journal of Respiratory Cell and Molecular Biology, American Journal of Respiratory Cell and Molecular Biology, American Thoracic Society, 2007, 36 (5), pp.615-624. ⟨10.1165/rcmb.2006-0200OC⟩
- Publication Year :
- 2007
- Publisher :
- HAL CCSD, 2007.
-
Abstract
- (IF : 4,608); International audience; Chronic lung inflammation in cystic fibrosis (CF) is specifically characterized by predominant endobronchial neutrophil infiltrates, colonization by Pseudomonas aeruginosa, and elevated levels of cytokines and chemokines, first of all IL-8. The extensive inflammatory process in CF lungs is the basis of progressive tissue damage and is largely considered detrimental, making antiinflammatory approaches a relevant therapeutic target. This neutrophil-dominated inflammation seems to be related to an excessive proinflammatory signaling, originating from the same surface epithelial cells expressing the defective CF transmembrane conductance regulator (CFTR) protein, although the underlying mechanisms have not been completely elucidated. To investigate the relationship between defective CFTR and the inflammatory response to P. aeruginosa in CF airway cells, we studied the effect of the DeltaF508 CFTR corrector, benzo(c)quinolizinium (MPB)-07 (Dormer et al., J Cell Science 2001;114:4073-4081). CF bronchial epithelial IB3-1 and CuFi-1 cells overproduced the inflammatory molecules, IL-8 and intercellular adhesion molecule (ICAM)-1, in response to P. aeruginosa, compared with the wild-type, CFTR-expressing bronchial cells, S9, and NuLi-1 cells. In both IB3-1 and CuFi-1 cells, the corrector MPB-07 dramatically reduces the IL-8 and ICAM-1 mRNA expression elicited by P. aeruginosa infection. Correction of CFTR-dependent Cl- efflux was confirmed in MPB-07-treated IB3-1 and CuFi-1 cells. In conclusion, the DeltaF508 CFTR corrector MPB-07 produces an antiinflammatory effect in CF bronchial cells exposed to P. aeruginosa in vitro.
- Subjects :
- cystic fibrosis • inflammation • Pseudomonas aeruginosa
[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
respiratory system
[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract
respiratory tract diseases
Subjects
Details
- Language :
- English
- ISSN :
- 10441549 and 15354989
- Database :
- OpenAIRE
- Journal :
- American Journal of Respiratory Cell and Molecular Biology, American Journal of Respiratory Cell and Molecular Biology, American Thoracic Society, 2007, 36 (5), pp.615-624. ⟨10.1165/rcmb.2006-0200OC⟩
- Accession number :
- edsair.dedup.wf.001..d47803fcd63d7683895063901557ec97