title: Interferon-gamma activates outwardly rectifying chloride channels in the human bronchial epithelial cell line BEAS-2B.
abstract: The mechanism of increased chloride currents by inflammatory cytokine, interferon-gamma (IFN-gamma), was investigated in cultured a human bronchial epithelial cell line (BEAS-2B) using cell-attached and inside-out patch configurations. The channel sensitive to chloride ion was activated by forskolin, an activator of adenylate cyclase, or 100 microM dibutyryl 5'-cyclic monophosphate in cell-attached configurations. The conductance of this channel was 40 +/- 4 pS in symmetrical 150 mM chloride solution between membrane potentials of 0 to  mV, and this channel was blocked by 500 microM 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), suggesting that this channel was an outwardly rectifying chloride channel (ORCC). Treatment of 10-1000 U/ml IFN-gamma for 3 hours, but not IFN-alpha, significantly increased channel activities of ORCC, and this activation was observed at least 24 hours after treatment. Erythromycin, a macrolide antibiotic, at a concentration of 100 microM inhibited the activation of ORCC induced by IFN-gamma. The findings of the present study indicate that increased mucus secretion during inflammation might be partly due to activation of chloride permeability by cytokine and erythromycin might improve oversecretion of mucus from bronchial epithelium by blocking ORCC.
authors: Third Department of Internal Medicine, University of Tokushima School of Medicine, Tokushima, Japan.
authors: N
authors: N
authors: Ge
authors: Y
authors: Y
authors: Nakamura
authors: Y
authors: Y
authors: Nakaya
authors: S
authors: S
authors: Sone
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000276:immunology*; D002461:Cell Line, Transformed; D018118:Chloride Channels / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D004917:Erythromycin / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D020545:Respiratory Mucosa
chemical_list: D018118:Chloride Channels; D004917:Erythromycin; D007371:Interferon-gamma