Document Detail

Does the F508-CFTR mutation induce a proinflammatory response in human airway epithelial cells?
MedLine Citation:
PMID:  22821996     Owner:  NLM     Status:  MEDLINE    
In the clinical setting, mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene enhance the inflammatory response in the lung to Pseudomonas aeruginosa (P. aeruginosa) infection. However, studies on human airway epithelial cells in vitro have produced conflicting results regarding the effect of mutations in CFTR on the inflammatory response to P. aeruginosa, and there are no comprehensive studies evaluating the effect of P. aeruginosa on the inflammatory response in airway epithelial cells with the ΔF508/ΔF508 genotype and their matched CF cell line rescued with wild-type (wt)-CFTR. CFBE41o- cells (ΔF508/ΔF508) and CFBE41o- cells complemented with wt-CFTR (CFBE-wt-CFTR) have been used extensively as an experimental model to study CF. Thus the goal of this study was to examine the effect of P. aeruginosa on gene expression and cytokine/chemokine production in this pair of cells. P. aeruginosa elicited a more robust increase in cytokine and chemokine expression (e.g., IL-8, CXCL1, CXCL2 and TNF-α) in CFBE-wt-CFTR cells compared with CFBE-ΔF508-CFTR cells. These results demonstrate that CFBE41o- cells complemented with wt-CFTR mount a more robust inflammatory response to P. aeruginosa than CFBE41o-ΔF508/ΔF508-CFTR cells. Taken together with other published studies, our data demonstrate that there is no compelling evidence to support the view that mutations in CFTR induce a hyperinflammatory response in human airway epithelial cells in vivo. Although the lungs of patients with CF have abundant levels of proinflammatory cytokines and chemokines, because the lung is populated by immune cells and epithelial cells there is no way to know, a priori, whether airway epithelial cells in the CF lung in vivo are hyperinflammatory in response to P. aeruginosa compared with non-CF lung epithelial cells. Thus studies on human airway epithelial cell lines and primary cells in vitro that propose to examine the effect of mutations in CFTR on the inflammatory response to P. aeruginosa have uncertain clinical significance with regard to CF.
Thomas H Hampton; Alicia E Ballok; Jennifer M Bomberger; Melanie R Rutkowski; Roxanna Barnaby; Bonita Coutermarsh; José R Conejo-Garcia; George A O'Toole; Bruce A Stanton
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-20
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  303     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-17     Completed Date:  2012-11-29     Revised Date:  2013-09-17    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L509-18     Citation Subset:  IM    
Dept. of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
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MeSH Terms
Cell Line
Cystic Fibrosis / immunology,  physiopathology*
Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
Cytokines / biosynthesis*
Epithelial Cells / immunology*
Interleukin-8 / biosynthesis
Lung / metabolism
Pseudomonas Infections / immunology
Pseudomonas aeruginosa / physiology*
Tumor Necrosis Factor-alpha / biosynthesis
Grant Support
Reg. No./Substance:
0/Cytokines; 0/Interleukin-8; 0/Tumor Necrosis Factor-alpha; 0/cystic fibrosis transmembrane conductance regulator delta F508; 126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator

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