Interleukin-13 induces a hypersecretory ion transport phenotype in human bronchial epithelial cells.
Interleukin (IL)-13 has been associated with asthma, allergic rhinitis, and chronic sinusitis, all conditions where an imbalance in epithelial fluid secretion and absorption could impact upon the disease. We have investigated the effects of IL-13 on the ion transport characteristics of human bronchial epithelial cells cultured at an apical-air interface. Ussing chamber studies indicated that 48 h pretreatment with IL-13 or IL-4 significantly reduced the basal short-circuit current (I(sc)) and inhibited the amiloride-sensitive current by >98%. Furthermore, the I(sc) responses were increased by more than six- and twofold over control values when stimulated with UTP or forskolin, respectively, after cytokine treatment. The IL-13-enhanced response to UTP/ionomycin was sensitive to bumetanide and DIDS and was reduced in a low-chloride, bicarbonate-free solution. Membrane permeablization studies indicated that IL-13 induced the functional expression of an apical Ca(2+)-activated anion conductance and that changes in apical or basolateral K(+) conductances could not account for the increased I(sc) responses to UTP or ionomycin. The results indicate that IL-13 converts the human bronchial epithelium from an absorptive to a secretory phenotype that is the result of loss of amiloride-sensitive current and an increase in a DIDS-sensitive apical anion conductance.
Danahay
Henry
H
Novartis Respiratory Research Centre, Horsham, West Sussex RH12 5AB, United Kingdom. henry.danahay@pharma.novartis.com
Atherton
Hazel
H
Jones
Gareth
G
Bridges
Robert J
RJ
Poll
Christopher T
CT
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D001249:Asthma / Q000378:metabolism; D001826:Body Fluids / Q000378:metabolism; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D020397:Goblet Cells / Q000166:cytology; D006801:Humans; D018793:Interleukin-13 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D011188:Potassium / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D014544:Uridine Triphosphate / Q000494:pharmacology
D002712:Chlorides; D004232:Diuretics; D018793:Interleukin-13; D007476:Ionophores; D002034:Bumetanide; D005576:Colforsin; D015847:Interleukin-4; D015759:Ionomycin; D000584:Amiloride; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D011188:Potassium; D002118:Calcium; D014544:Uridine Triphosphate