Anti-inflammatory effect of miglustat in bronchial epithelial cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Cystic Fibrosis Année : 2008

Anti-inflammatory effect of miglustat in bronchial epithelial cells

Résumé

The role of CFTR deficiency in promoting inflammation remains unclear. Perez et al. [A. Perez, A.C. Issler, C.U. Cotton, T.J. Kelley, A.S. Verkman and P.B. Davis, CFTR inhibition mimics the cystic fibrosis inflammatory profile. Am J Physiol Lung Cell Mol Physiol 2007; 292:L383– L395.] recently demonstrated that the inhibition of function of w/t CFTR produces an inflammatory profile that resembles that observed in CF patients, whereas we found that correction of F508del-CFTR function with MPB-07 down-modulates the inflammatory response to P. aeruginosa in CF bronchial cells [M.C. Dechecchi, E. Nicolis, V. Bezzerri, A. Vella, M. Colombatti, B.M. Assael, et al., MPB-07 reduces the inflammatory response to Pseudomonas aeruginosa in cystic fibrosis bronchial cells. Am J Respir Cell Mol Biol 2007; 36, 615–624.]. Since both evidence support a link between CFTR function and inflammation, we extended our investigation to other F508del-CFTR correctors, such as miglustat (Norez, 2006), an approved drug for Gaucher disease, in comparison with the galactose analogue NB-DGJ. We report here that miglustat but not NB-DGJ restores F508del-CFTR function in CF bronchial epithelial IB3-1 and CuFi-1 cells. Miglustat and NB-DGJ reduce the inflammatory response to P. aeruginosa in both CF and non-CF bronchial cells, indicating that the anti-inflammatory effect is independent of the correction of F508del-CFTR function. Miglustat also inhibits the inflammatory response induced by the supernatant of mucopurulent material obtained from the lower airway tract of cystic fibrosis patients with chronic bacterial colonization (Ribeiro, 2005). Both compounds do not interfere with the adherence of P. aeruginosa to the cells and reduce the expression of IL-8 not only after challenge with P. aeruginosa but also after exposure to TNF alpha or IL-1 beta, suggesting an effect on transduction proteins downstream and in common with different receptors for pathogens. Finally, miglustat has no major effects on overall binding activity of transcription factors NF-κBNF-kB and AP-1. Since miglustat is an approved drug, it could be investigated as a novel anti-inflammatory molecule to ameliorate lung inflammation in CF patients. © 2008 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Dates et versions

hal-00392599 , version 1 (08-06-2009)

Identifiants

Citer

Maria Cristina Decheccchi, Elena Nicolis, Caroline Norez, Valentino Bezzerri, Monica Borgatti, et al.. Anti-inflammatory effect of miglustat in bronchial epithelial cells. Journal of Cystic Fibrosis, 2008, 7 (6), pp.555-565. ⟨10.1016/j.jcf.2008.06.002⟩. ⟨hal-00392599⟩
177 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More