Journal
JOURNAL OF CYSTIC FIBROSIS
Volume 10, Issue 2, Pages 107-113Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jcf.2010.11.005
Keywords
Cytokines; Reactive oxygen species; MAPK; Cystic fibrosis; Gene expression
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Funding
- Canadian Cystic Fibrosis Foundation
- Department of Medicine, McGill University
- McGill University Health Centre Research Institute (MUHC-RI)
- Canadian Foundation for Innovation
- Les Fonds de la Recherche en Sante du Quebec (FRSQ)
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Background: Understanding the mechanisms underlying bacterial-driven inflammation and neutrophil recruitment is important to design better therapies for CF. CXCL8 is an important chemokine found elevated in the airways of CF patients that recruits neutrophil to sites of the inflammation. Methods: Airway epithelial cells (AECs) expressing wild-type CFTR or CFTR Delta F508 were challenged with Pseudomonas aeruginosa diffusible material (PsaDM) and the synthesis of CXCL8 was measured by quantitative real-time PCR and ELISA in absence or presence of MAPK inhibitors, TLR antagonists, glutathione and a NADPH oxidase inhibitor. Results: CFTR Delta F508 AECs secrete more CXCL8 in response to PsaDM than their wild type counterpart, which can be reversed by addition of extracellular glutathione or incubating AECs at 27 degrees C to favour folding and expression of CFTR at the cell membrane. Moreover, in CFTR Delta F508 AECs, TLR2, T1R4 and TLR5 act redundantly to drive CXCL8 synthesis via the activation of NADPH oxidase. Discussions: These results demonstrate that NADPH oxidase is necessary for CXCL8 synthesis in response to TLRs activation by P. aeruginosa. (C) 2010 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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