IL-4 is a potent modulator of ion transport in the human bronchial epithelium in vitro.
Recent data show that proinflammatory stimuli may modify significantly ion transport in the airway epithelium and therefore the properties of the airway surface fluid. We have studied the effect of IL-4, a cytokine involved in the pathogenesis of asthma, on transepithelial ion transport in the human bronchial epithelium in vitro. Incubation of polarized bronchial epithelial cells with IL-4 for 6-48 h causes a marked inhibition of the amiloride-sensitive Na(+) channel as measured in short circuit current experiments. On the other hand, IL-4 evokes a 2-fold increase in the current activated by a cAMP analog, which reflects the activity of the cystic fibrosis transmembrane conductance regulator (CFTR). Similarly, IL-4 enhances the response to apical UTP, an agonist that activates Ca(2+)-dependent Cl(-) channels. These effects are mimicked by IL-13 and blocked by an antagonist of IL-4Ralpha. RT-PCR experiments show that IL-4 elicits a 7-fold decrease in the level of the gamma amiloride-sensitive Na(+) channel mRNA, one of the subunits of the amiloride-sensitive Na(+) channel, and an increase in CFTR mRNA. Our data suggest that IL-4 may favor the hydration of the airway surface by decreasing Na(+) absorption and increasing Cl(-) secretion. This could be required to fluidify the mucus, which is hypersecreted during inflammatory conditions. On the other hand, the modifications of ion transport could also affect the ion composition of airway surface fluid.
Galietta
Luis J V
LJ
Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova, Italy. galietta@unige.it
Pagesy
Patrick
P
Folli
Chiara
C
Caci
Emanuela
E
Romio
Leila
L
Costes
Bruno
B
Nicolis
Elena
E
Cabrini
Giulio
G
Goossens
Michel
M
Ravazzolo
Roberto
R
Zegarra-Moran
Olga
O
D001980:Bronchi / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002118:Calcium / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000096:biosynthesis / Q000235:genetics; D015194:Diffusion Chambers, Culture; D004306:Dose-Response Relationship, Immunologic; D053503:Epithelial Sodium Channels; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology*; D017136:Ion Transport / Q000235:genetics / Q000276:immunology; D009298:Nasal Polyps / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000096:biosynthesis / Q000235:genetics; D013499:Surface Properties
C505032:CFTR protein, human; D002712:Chlorides; D053503:Epithelial Sodium Channels; D012333:RNA, Messenger; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D015847:Interleukin-4; D007371:Interferon-gamma; D002118:Calcium