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Article Dans Une Revue European Journal of Pharmacology Année : 2012

Azithromycin fails to reduce inflammation in cystic fibrosis airway epithelial cells

Résumé

Cystic fibrosis is a hereditary disease caused by a mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene that encodes a chloride (a) channel. Cystic fibrosis pulmonary pathophysiology is characterised by chronic inflammation and bacterial infections. Azithromycin, a macrolide antibiotic, has shown promising anti-inflammatory properties in some inflammatory pulmonary diseases. Moreover, all clinical studies have presented an improvement of the respiratory condition of cystic fibrosis patients, but the molecular and cellular mechanisms remain unknown. The aim of this study was to investigate, in bronchial epithelial cells, the effects of azithromycin on inflammatory pathways involved in cystic fibrosis. We have analysed the effects of azithromycin on cystic fibrosis and non-cystic fibrosis bronchial epithelial cell lines but also in non-immortalized non-cystic fibrosis human glandular cells. To create an inflammatory context, cells were treated with Tumor Necrosis Factor (TNF)-alpha or Interleukin (IL)1-beta. Activation of the NF-kappa B pathway was investigated by luciferase assay, western blotting, and by Forster Resonance Energy Transfer imaging, allowing the detection of the interaction between the transcription factor and its inhibitor in live cells. In all conditions tested, azithromycin did not have an anti-inflammatory effect on the cystic fibrosis human bronchial epithelial cells and on CFTR-inhibited primary human bronchial glandular cells. More, our data showed no effect of azithromycin on IL-1 beta- or TNF-alpha-induced IL-8 secretion and NF-kappa B pathway activation. Taken together, these data show that azithromycin is unable to decrease in vitro inflammation in cystic fibrosis cells from airways
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Dates et versions

hal-02398074 , version 1 (06-12-2019)

Identifiants

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Vinciane Saint-Criq, Manon Ruffin, Carine Rebeyrol, Loïc Guillot, Jacky Jacquot, et al.. Azithromycin fails to reduce inflammation in cystic fibrosis airway epithelial cells. European Journal of Pharmacology, 2012, 674 (1), pp.1-6. ⟨10.1016/j.ejphar.2011.10.027⟩. ⟨hal-02398074⟩
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