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Articles in PresS, published online ahead of print October 5, 2001
Am J Physiol Lung Cell Mol Physiol, 10.1152/ajplung.00311.2001
Submitted on August 7, 2001
Accepted on October 3, 2001
1 Biology III, Novartis Horsham Research Centre, Horsham, West Sussex, United Kingdom
2 Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA, USA
* To whom correspondence should be addressed. E-mail: henry.danahay{at}pharma.novartis.com.
Increased production of the Th2 cytokine IL-13 has been demonstrated in asthma, allergic rhinitis and chronic sinusitis, all conditions where an imbalance in epithelial fluid secretion and absorption could impact upon the disease. To this end we have investigated the effects of IL-13 on the ion transport characteristics of human bronchial epithelial cells (HBECs) cultured at an apical air interface to form a differentiated mucociliary phenotype. Ussing chamber studies indicated that IL-13 (10 ng/mL, 48h) and IL-4 (10 ng/mL, 48h) significantly reduced the basal short circuit current (ISC) and inhibited the amiloride-sensitive current by >98%. Furthermore, the ISC responses were increased by >6 fold and 2-fold over control values following stimulation with UTP or forskolin respectively in the cytokine treated cells. The IL-13 enhanced response to either UTP or ionomycin was sensitive to bumetanide (60 µM, basolateral) and DIDS (300 µM, apical) and was reduced in a low-chloride, bicarbonate-free solution. Selective permeablisation of either the apical or basolateral membrane indicated that IL-13 pre-treatment induced the functional expression of an apical Ca2+ activated anion conductance and that changes in apical or basolateral K+ conductances could not account for the increased ISC responses to UTP or ionomycin. The results indicate that IL-13 treatment converts the human bronchial epithelium from an absorptive to a secretory phenotype that is due to loss of amiloride-sensitive current and an increase in a DIDS-sensitive apical anion conductance.
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