Published ahead of print on June 26, 2003, doi:10.1164/rccm.200212-1437OC Am. J. Respir. Crit. Care Med., Volume 168, Number 5, September 2003, 581-587 A more recent version of this article appeared on September 1, 2003
Submitted on December 11, 2002 In vivo and in vitro effects of macrolide antibiotics on mucus secretion in airway epithelial cellsTakeshi Shimizu1*,1 Otorhinolaryngology and Third Department of Internal Medicine, Mie University School of Medicine, Tsu, Mie, Japan * To whom correspondence should be addressed. 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 in ovalbumin-sensitized rats, and by intranasal lipopolysaccharide instillation. Oral administration of clarithromycin (5-10mg/kg) significantly inhibited ovalbumin- and lipopolysaccharide-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 enzyme-linked immunosorbent assay using anti-mucin monoclonal antibodies (anti-MUC5AC and HCS18). Clarithromycin and erythromycin significantly inhibited spontaneous and tumor necrosis factor- Key words: ovalbumin, lipopolysaccharide, goblet cell, nose
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(20ng/ml)-induced mucus secretion from NCI-H292 cells at 10-6-10-7M, and from human nasal epithelial cells at 10-4-10-5M. MUC5AC mRNA expression was also significantly inhibited. These results indicate that 14 member macrolide antibiotics, clarithromycin 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 lipopolysaccharide stimulation.
