| Title | MPB-07 Reduces the Inflammatory Response to Pseudomonas aeruginosa in CF Bronchial Cells. | | Author(s) | Dechecchi MC, Nicolis E, Bezzerri V, Vella A, Colombatti M, Assael BM, Mettey Y, Borgatti M, Mancini I, Gambari R, Becq F, Cabrini G | | Institution | Laboratory of Molecular Pathology, Cystic Fibrosis Center, University Hospital of Verona, Verona, Italy. | | Source | Am J Respir Cell Mol Biol 2006 Dec 29. | | Abstract | Chronic lung inflammation in cystic fibrosis (CF) is specifically characterized by predominant endobronchial neutrophil infiltrates, colonization by Pseudomonas aeruginosa (P.aeruginosa) and elevated levels of cytokines and chemokines, first of all interleukin (IL)-8. The extensive inflammatory process in CF lungs is the basis of progressive tissue damage and is largely considered detrimental, making anti-inflammatory approaches a relevant therapeutic target. This neutrophil-dominated inflammation seems to be related to an excessive pro-inflammatory signalling 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 MPB-07 (Dormer et al., J Cell Science 114, 4073-4081, 2001). CF bronchial epithelial IB3-1 and CuFi-1 cells over-produced the inflammatory molecules IL-8 and InterCellular Adhesion Molecule (ICAM)-1 in response to P.aeruginosa, compared with the w/t CFTR expressing bronchial cells S9 and NuLi-1 cells. In both IB3 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 anti-inflammatory effect in CF bronchial cells exposed to P.aeruginosa in vitro. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 17197571 |
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