Modification of transepithelial ion transport in human cultured bronchial epithelial cells by interferon-gamma.
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 Ca(2+)-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.
Galietta
L J
LJ
Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, 16148 Genoa, Italy. galietta@unige.it
Folli
C
C
Marchetti
C
C
Romano
L
L
Carpani
D
D
Conese
M
M
Zegarra-Moran
O
O
D001692:Biological Transport / Q000187:drug effects; D001826:Body Fluids / Q000378:metabolism; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D003550:Cystic Fibrosis / Q000378:metabolism / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D015536:Down-Regulation; D004553:Electric Conductivity; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007477:Ions; D012016:Reference Values; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
C505032:CFTR protein, human; D018118:Chloride Channels; D007477:Ions; D015222:Sodium Channels; D014409:Tumor Necrosis Factor-alpha; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D007371:Interferon-gamma; D000242:Cyclic AMP; D002118:Calcium; D014544:Uridine Triphosphate