Increased chloride efflux in colchicine-resistant airway epithelial cell lines.
Colchicine has been proposed as a treatment to alleviate chronic lung inflammation in cystic fibrosis patients and clinical trials are ongoing. Our aim was to investigate whether chronic exposure of cystic fibrosis cells to colchicine can affect their ability to transport chloride in response to cAMP. Colchicine-resistant cells were selected by growing in medium containing nanomolar concentrations of the drug. While microtubuli were affected by acute exposure to colchicine, they appeared normal in colchicine-resistant cells. Colchicine-resistant clones had higher expression of multidrug resistance proteins compared to untreated cells. Cystic fibrosis transmembrane conductance regulator (CFTR) labelling by immunocytochemistry showed no significant changes. The intracellular chloride concentration and basal chloride efflux of the cystic fibrosis treated cells increased significantly compared with untreated cells, while for the cAMP-stimulated Cl-efflux there was no significant change. The results suggest that colchicine promotes chloride efflux via alternative chloride channels. Since this is an accepted strategy for pharmacological treatment of cystic fibrosis, the results strengthen the notion that colchicine would be beneficial to these patients.
Dragomir
Anca
A
Department of Medical Cell Biology, University of Uppsala, Box 571, 751 23 Uppsala, Sweden. anca.dragomir@medcellbiol.uu.se
Roomans
Godfried M
GM
D001692:Biological Transport; D001980:Bronchi / Q000473:pathology; D002712:Chlorides / Q000378:metabolism*; D003078:Colchicine / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects; D018432:Drug Resistance, Multiple; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism
D002712:Chlorides; D003078:Colchicine; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C505032:CFTR protein, human