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Updated: Aug 8, 2026
Culturing of Human Nasal Epithelial Cells at the Air Liquid Interface
Published on: October 9, 2013
Interferon-gamma activates outwardly rectifying chloride channels in the human bronchial epithelial cell line BEAS-2B
1Third Department of Internal Medicine, University of Tokushima School of Medicine, Tokushima, Japan.
Insights
Interferon-gamma (IFN-gamma) activates outwardly rectifying chloride channels (ORCC) in bronchial cells, increasing chloride currents. Erythromycin inhibits this activation, potentially reducing mucus hypersecretion during inflammation.
Area of Science:
- Cellular physiology
- Molecular biology
- Respiratory medicine
Background:
- Inflammatory cytokines like interferon-gamma (IFN-gamma) play a role in respiratory diseases.
- Altered chloride ion transport is implicated in conditions such as cystic fibrosis and asthma.
- Understanding the mechanisms of cytokine-induced ion channel modulation is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the mechanism by which IFN-gamma increases chloride currents in human bronchial epithelial cells.
- To identify the specific chloride channel involved and its regulation by IFN-gamma.
- To evaluate the potential therapeutic effect of erythromycin on IFN-gamma-induced chloride channel activation.
Main Methods:
- Utilized cell-attached and inside-out patch clamp electrophysiology on cultured human bronchial epithelial cells (BEAS-2B).
- Characterized the biophysical properties and pharmacological profile of the identified chloride channel.
- Assessed the effect of IFN-gamma and IFN-alpha treatment on channel activity.
- Examined the inhibitory effect of erythromycin on IFN-gamma-induced channel activation.
Main Results:
- Identified and characterized an outwardly rectifying chloride channel (ORCC) with a conductance of 40 ± 4 pS, blocked by DIDS.
- Demonstrated that IFN-gamma significantly increased ORCC activity in a dose- and time-dependent manner, with effects lasting at least 24 hours.
- Showed that IFN-alpha did not affect ORCC activity.
- Found that erythromycin (100 μM) inhibited the IFN-gamma-induced activation of ORCC.
Conclusions:
- IFN-gamma activates ORCC in human bronchial epithelial cells, contributing to increased chloride permeability.
- This cytokine-induced channel activation may play a role in the excessive mucus secretion observed during airway inflammation.
- Erythromycin's ability to inhibit ORCC activation suggests a potential therapeutic strategy for managing mucus hypersecretion in respiratory inflammatory conditions.
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.
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