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Am J Physiol Lung Cell Mol Physiol 278: L1186-L1194, 2000;
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Vol. 278, Issue 6, L1186-L1194, June 2000

Modification of transepithelial ion transport in human cultured bronchial epithelial cells by interferon-gamma

Luis J. V. Galietta1, Chiara Folli1, Carla Marchetti2, Luca Romano3, Daniela Carpani4, Massimo Conese4, and Olga Zegarra-Moran1

1 Laboratorio di Genetica Molecolare and 3 Clinica Pediatrica, Istituto Giannina Gaslini, 16148 Genoa; 2 Istituto di Cibernetica e Biofisica, Consiglio Nazionale delle Ricerche, 16149 Genoa; and 4 Telethon Institute for Gene Therapy, Ospedale San Raffaele, 20132 Milan, Italy

Human bronchial epithelial cells were treated in vitro with interferon-gamma or tumor necrosis factor-alpha to assess their effect on transepithelial ion transport. Short-circuit current measurements revealed that Na+ absorption was markedly inhibited by interferon-gamma (10-1,000 U/ml). The cystic fibrosis transmembrane conductance regulator was also downregulated by interferon-gamma as evident at the protein level and by the decrease in the cAMP-dependent current. On the other hand, interferon-gamma caused an increase of the current elicited by apical UTP application, which is due to the activity of Ca2+-dependent Cl- channels. Tumor necrosis factor-alpha caused few changes in ion transport. Transepithelial fluid transport was measured in normal and cystic fibrosis cells. At rest, both types of cells showed an amiloride-sensitive fluid absorption that was inhibited by interferon-gamma but not by tumor necrosis factor-alpha . Our results show that interferon-gamma alters the transepithelial ion transport of cultured bronchial cells. This effect may change the ion composition and/or volume of periciliary fluid.

airway surface fluid; sodium absorption; cystic fibrosis; airway epithelium; chloride transport


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