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ENaC, iNOS, mucins expression, and wound healing in cystic fibrosis airway epithelial and submucosal cells
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. (Prof. Godfried M Roomans)ORCID iD: 0000-0003-4946-3228
2013 (English)Manuscript (preprint) (Other academic)
Abstract [en]

with endogenous wild-type cystic fibrosis transmembrane conductance regulator (CFTR), CFBE cells with mutated ΔF508-CFTR, corrected CFBE cells overexpressing CFTR, CFSME (CF submucosal) and Calu-3 (non-CF submucosal) cells with respect to the epithelial sodium channel (ENaC), inducible NO synthase (iNOS), and mucins (MUC) (studied by quantitative Real-Time-Polymerase Chain Reaction, qRT-PCR, and Western blot), and wound healing.

CFBE cells had significantly more expression of b- and g-ENaC mRNA and of b-ENaC protein than 16HBE cells. Compared to corrected CFBE cells, CFBE cells had increased mRNA expression of all ENaC subunits and b-ENaC protein. For ENaC, the CFSME/Calu-3 mRNA ratio was very low and contradictory to the ENaC upregulation in CF cells. CFBE cells showed decreased expression of iNOS at both mRNA and protein levels compared to 16HBE cells and only at the mRNA level compared to corrected CFBE cells. CFSME cells showed expression of iNOS whereas Calu-3 cells did not. Higher expression of MUC2 and MUC5B was found in corrected CFBE cells compared to CFBE cells. Wound healing in CFBE cells was delayed compared to corrected CFBE cells, but not to 16HBE cells, and in CFSME cells compared to Calu-3 cells.

Our data suggest CFSME as an inappropriate CF cell model for Calu-3 cells, and provide only partial support for the theory that the differences (in ENaC, iNOS, mucins, and wound healing) between these cell lines are associated to the presence of CFTR in the bronchial airway epithelial cells.

Place, publisher, year, edition, pages
2013.
Keywords [en]
Cystic fibrosis, CFTR, ENaC, iNOS, mucin, wound healing, CFTR inh-172
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-32765OAI: oai:DiVA.org:oru-32765DiVA, id: diva2:679018
Funder
Swedish Heart Lung FoundationAvailable from: 2013-12-13 Created: 2013-12-13 Last updated: 2018-04-23Bibliographically approved
In thesis
1. Cell responses in infected and cystic fibrosis respiratory epithelium
Open this publication in new window or tab >>Cell responses in infected and cystic fibrosis respiratory epithelium
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Respiratory Epithelium. Örebro Studies in Medicine 99. Cystic fibrosis (CF) is caused by a mutation in a cAMP-activated chloride (Cl-) channel (CFTR). Mortality and morbidity in CF is mainly due to the deregulated responses of the airway epithelial cells. The purpose of the thesis was to investigate the behaviour of the airway epithelial cells that are involved in maintaining the homeostasis in the airways.

Nasal brush biopsies obtained from anesthetized human nasal mucosa can be an easy source to establish primary epithelial cell lines (Paper I). We found that CF and non CF cellular models cannot fully show the relation between CFTR and the phenotypic differences between CF and healthy cells (Paper II). The possibility to correct the Cl- transport defect in CF by the use of stable NOdonors, and ambroxol was investigated. NO-donors stimulated Cl- efflux, and decreased ENaC mRNA expression in CFBE cells (Paper III), while ambroxol increased Cl- efflux from CFBE cells, and showed a positive effect on the biosynthesis of CFTR (Paper IV). This suggests that these substances may be a potentially interesting group of compounds for the treatment of CF. Increased levels of IL-6 and IL-8 upon infection in CF cells can increase the susceptibility of P. aeruginosa infected CF cells to apoptosis and/or internalization of these bacteria in CF cells and hence, may have important roles in the pathology of P. aeruginosa infection in CF airways. If internalization is beneficial for the host then glucocorticoids (GCs) are not beneficial for the treatment of CF patients. However, GCs may improve airway hydration. Whether the benefits of GC treatment outweigh the negative effects is questionable, and further clinical studies need to be carried out (Paper V). The neonatal isolates S. epidermidis 94B080 and S. aureus 90B083 can modulate CFTR and ENaC expression in airway epithelial cells, which may disturb the ion transport in the respiratory epithelium upon bacterial exposure. Airway epithelial cells also show excessive inflammatory responses to these bacteria, which means that these bacteria may induce pulmonary inflammation (Paper VI).

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2014. p. 85
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 99
Keywords
airway epithelial cells, cystic fibrosis, bacterial infection, CFTR, ENaC, chloride transport, intracellular calcium, P. aeruginosa internalization
National Category
Biomedical Laboratory Science/Technology
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-32191 (URN)978-91-7668-984-4 (ISBN)
Public defence
2014-01-17, Bohmansalen, B-huset, Universitetssjukhuset i Örebro, S Grev Rosengatan 18, 703 62 Örebro, 11:57 (Swedish)
Opponent
Supervisors
Available from: 2013-10-29 Created: 2013-10-29 Last updated: 2017-10-17Bibliographically approved

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Hussain, Rashida

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