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The effect of ambroxol on chloride transport and mRNA expression of CFTR and ENaC in cystic fibrosis airway epithelial cells
Örebro University, School of Health and Medical Sciences.
Örebro University, School of Health and Medical Sciences.
Örebro University, School of Health and Medical Sciences.
Örebro University, School of Health and Medical Sciences.
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(English)Manuscript (preprint) (Other academic)
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-20478OAI: oai:DiVA.org:oru-20478DiVA, id: diva2:461550
Available from: 2011-12-05 Created: 2011-12-05 Last updated: 2017-10-17Bibliographically approved
In thesis
1. Chloride transport and inflammation in cystic fibrosis airways
Open this publication in new window or tab >>Chloride transport and inflammation in cystic fibrosis airways
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cystic fibrosis (CF) is one of the most common lethal, autosomal recessive inherited diseases among Caucasians. It is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel activated by cyclic AMP. The disturbed electrolyte transport caused by the impaired CFTR channel leads to defective mucociliary clearance, airway obstruction and chronic airway infections.

Three different substances (N-acetylcysteine, duramycin and ambroxol) were tested in order to investigate if they could improve Cl- transport across epithelia and if so, through which mechanisms.

N-acetylcysteine (NAC), a well-known mucolytic and anti-oxidant drug increased significantly Cl-efflux from cystic fibrosis bronchial epithelial (CFBE) cells. It was shown that NAC can (partially) correct the Cl- transport deficiency in CF airway epithelial cells withF508-CFTR through a direct effect on CFTR (Paper I).

Duramycin increased Cl- efflux from CF airway epithelial cell in a very narrow concentration range. That effect is not associated with an increase in the intracellular calcium concentration (Paper II). The fact that results of a clinical study of duramycin, carried out several years ago, have not been published suggests that duramycin is not only ineffective in vitro, but also in vivo.

Ambroxol has been widely used as supplementary therapy for the treatment of many respiratory diseases. It was shown that 8h treatment with ambroxol caused a nearly six-fold increase of Cl- efflux from CF airway epithelial cells, which brings the Cl- efflux up to the level of cells with wild-type CFTR (Paper III).

Moreover, we studied the role of the innate immunity system in CF airway epithelial cells. High levels of Nod1 were found both in CF and non-CF airway epithelial cells, but a decreased expression of Nod2, and decreased levels of the pro-inflammatory cytokines IL-6 and IL-8 were found in CF airway epithelial cells compared to non-CF cells. The decreased levels of Nod2 suggest that the CF-cells are less able to recognize pathogens such as Pseudomonas aeruginosa, which might lead to a higher uptake of the pathogen (Paper IV).

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2011. p. 65
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 62
Keywords
Cystic fibrosis, CFTR, chloride efflux, N-acetylcysteine, ambroxol, duramycin, Nod-like receptors, cytokines
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:oru:diva-19126 (URN)978-91-7668-830-4 (ISBN)
Public defence
2011-11-25, Seminarierum Berguven (F1), Universitetssjukhuset, Örebro, 13:00 (English)
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Supervisors
Available from: 2011-10-04 Created: 2011-10-04 Last updated: 2017-10-17Bibliographically approved

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Varelogianni, GeorgiaStrid, HiljaOliynyk, IgorRoomans, Godfried M.Johannesson, Marie

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CiteExportLink to record
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