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MPB-07 reduces the inflammatory response to Pseudomonas aeruginosa in cystic fibrosis bronchial cells.
- Source :
-
American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2007 May; Vol. 36 (5), pp. 615-24. Date of Electronic Publication: 2006 Dec 29. - Publication Year :
- 2007
-
Abstract
- 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 :
- Bronchi microbiology
Chlorides metabolism
Cyclic AMP metabolism
Cystic Fibrosis immunology
Cystic Fibrosis Transmembrane Conductance Regulator metabolism
Epithelial Cells drug effects
Epithelial Cells immunology
Epithelial Cells microbiology
Epithelial Cells pathology
Gene Expression Regulation drug effects
Genistein pharmacology
Humans
Intercellular Adhesion Molecule-1 genetics
Intercellular Adhesion Molecule-1 metabolism
Interleukin-8 genetics
Interleukin-8 metabolism
NF-kappa B metabolism
Protein Binding drug effects
Pseudomonas Infections
RNA, Messenger genetics
RNA, Messenger metabolism
Transcription Factor AP-1 metabolism
Transcription, Genetic drug effects
Anti-Inflammatory Agents pharmacology
Bronchi immunology
Bronchi pathology
Cystic Fibrosis microbiology
Cystic Fibrosis pathology
Pseudomonas aeruginosa immunology
Quinolizines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1044-1549
- Volume :
- 36
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of respiratory cell and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 17197571
- Full Text :
- https://doi.org/10.1165/rcmb.2006-0200OC