In vivo and in vitro effects of macrolide antibiotics on mucus secretion in airway epithelial cells.
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-alpha (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.
Shimizu
Takeshi
T
Department of Otorhinolaryngology, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514, Japan. tshimizu@clin.medic.mie-u.ac.jp
Shimizu
Shino
S
Hattori
Reiko
R
Gabazza
Esteban C
EC
Majima
Yuichi
Y
D000667:Ampicillin / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018277:Carcinoma, Mucoepidermoid / Q000378:metabolism / Q000648:ultrastructure; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D017291:Clarithromycin / Q000494:pharmacology*; D004195:Disease Models, Animal; D020397:Goblet Cells / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D066298:In Vitro Techniques; D015570:Josamycin / Q000494:pharmacology*; D008297:Male; D009093:Mucus / Q000187:drug effects* / Q000378:metabolism*; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D009669:Nose Neoplasms / Q000378:metabolism / Q000648:ultrastructure; D010406:Penicillins / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012130:Respiratory Hypersensitivity / Q000378:metabolism* / Q000473:pathology; D012636:Secretory Rate / Q000187:drug effects
D000900:Anti-Bacterial Agents; D010406:Penicillins; D000667:Ampicillin; D017291:Clarithromycin; D015570:Josamycin