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Colchicine increases the chloride efflux in airway epithelial cell lines.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
Article in journal (Refereed) Submitted
URN: urn:nbn:se:uu:diva-91156OAI: oai:DiVA.org:uu-91156DiVA: diva2:163784
Available from: 2003-12-17 Created: 2003-12-17Bibliographically approved
In thesis
1. Approaches to Pharmacological Treatment and Gene Therapy of Cystic Fibrosis
Open this publication in new window or tab >>Approaches to Pharmacological Treatment and Gene Therapy of Cystic Fibrosis
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cystic fibrosis (CF) is the most common lethal genetic disease in the white population. It is due to mutations in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR), a protein that functions mainly as a cAMP-activated chloride channel. The disease impairs ion and water transport in epithelia-lined organs such as airways, digestive tract, reproductive epithelium and sweat glands. At present the only therapy is symptomatic and development of curative treatment depends on uncovering the links between the defective CFTR and the disease, as well as on improving end-point measurements.

A method has been established for studying ion transport in an easily accessible cell type (nasal epithelial cells) from normal and cystic fibrosis patients by X-ray microanalysis. This method represents a rather simple and direct way of measuring simultaneously several chemical elements of biological interest.

Studies of chloride transport by means of a fluorescent indicator (MQAE) in nasal epithelial cells from CF patients showed that the phenotype cannot exclusively be explained by the CFTR activity in patients with severe genotype.

A common Portuguese CFTR mutation (A561E) causes protein mislocalization in the endoplasmic reticulum similar to the most common CF mutation (ΔF508) and thus it should be possible to treat it with the same pharmacological strategies.

Chronic treatment of CF airway epithelial cells with nanomolar concentrations of colchicine increased the chloride efflux via chloride channels other than CFTR, strengthening the notion that colchicine could be beneficial to CF patients.

Successful in vitro transfection of CF airway epithelial cells with cationic vectors was possible with short incubation times. Heparin added at the end of the transfection incubation time could help to maintain the viability of the cells, without interfering with the transfection efficiency. It seems possible that heparin could be an adjuvant for non-viral mediated gene therapy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 51 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1312
Anatomy, airway epithelium, colchicine, cystic fibrosis, chloride transport, genotype, heparin, phenotype, transfection, X-ray microanalysis, Anatomi
National Category
Cell and Molecular Biology
urn:nbn:se:uu:diva-3845 (URN)91-554-5822-X (ISBN)
Public defence
2004-01-16, B21, BMC, Husargatan 3, Uppsala, 13:15
Available from: 2003-12-17 Created: 2003-12-17Bibliographically approved

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