Published ahead of print on June 26, 2003, doi:10.1164/rccm.200212-1437OC
American Journal of Respiratory and Critical Care Medicine Vol 168. pp. 581-587, (2003)
© 2003 American Thoracic Society
In Vivo and In Vitro Effects of Macrolide Antibiotics on Mucus Secretion in Airway Epithelial Cells
Takeshi Shimizu,
Shino Shimizu,
Reiko Hattori,
Esteban C. Gabazza and
Yuichi Majima
Department of Otorhinolaryngology and Third Department of Internal Medicine, Mie University School of Medicine, Edobashi, Tsu, Mie, Japan
Correspondence and requests for reprints should be addressed to Takeshi Shimizu, M.D., Department of Otorhinolaryngology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514, Japan. E-mail: tshimizu{at}clin.medic.mie-u.ac.jp
To examine the in vivo effects of macrolide antibiotics on mucus hypersecretion, we induced hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium by intranasal instillation of ovalbumin (OVA) in OVA-sensitized rats and by intranasal LPS instillation. Oral administration of clarithromycin (CAM) (5–10 mg/kg) significantly inhibited OVA- and LPS-induced mucus production and neutrophil infiltration, whereas josamycin and ampicillin showed no effect. In vitro effects of macrolide antibiotics on airway epithelial cells were examined using NCI-H292 cells and human nasal epithelial cells cultured in air–liquid interface. Mucus secretion was evaluated by ELISA using anti-mucin monoclonal antibodies (anti-MUC5AC and HCS18). CAM and erythromycin significantly inhibited spontaneous and tumor necrosis factor– (20 ng/ml)–induced mucus secretion from NCI-H292 cells at 10-6 to 10-7 M and from human nasal epithelial cells at 10-4 to 10-5 M. MUC5AC messenger RNA expression was also significantly inhibited. These results indicate that the 14-member macrolide antibiotics, CAM and erythromycin, exert direct inhibitory effects on mucus secretion from airway epithelial cells and that they may be useful for the treatment of mucus hypersecretion caused by allergic inflammation and LPS stimulation.
Key Words: ovalbumin • lipopolysaccharide • goblet cell • nose
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