title: Enhancement of thioredoxin production from nasal epithelial cells by the macrolide antibiotic, clarithromycin in vitro.
abstract: Low-dose and long-term administration of 14-membered macrolide antibiotics is well-known to be effective in the treatment of chronic airway diseases. Although there is much evidence that the anti-inflammatory action, but not the anti-microbial action of macrolides, is responsible for the clinical efficacy of these agents on chronic airway inflammatory diseases, the precise therapeutic mechanisms are not well-understood. Since thioredoxin (TRX) has now attracted attention as an endogenous peptide with immunomodulatory effects, the present study was undertaken to examine whether macrolide antibiotics could favorably modulate the clinical status of such diseases via the production of TRX from nasal epithelial cells in vitro. Nasal epithelial cells (5×10(5) cells/ml) obtained from five patients were stimulated with 50 μM H2O2 in the presence of different concentrations of macrolide antibiotics for 24 h. TRX levels in culture supernatants were examined by enzyme-linked immunosorbent assay. We also examined the influence of macrolide antibiotics on TRX mRNA expression and mRNA translation by RT-PCR and a wheat germ cell-free protein synthesis technique, respectively. The addition of clarithromycin (CAM) to cell cultures caused an increase in the ability of cells to produce TRX in response to H2O2 stimulation, and the minimum concentration that caused a significant increase was 0.5 μg/ml. On the other hand, josamycin, a 16-membered macrolide antibiotic, did not increase TRX production induced by H2O2 stimulation. Although the treatment of cells with CAM inhibits TRX mRNA transcription, the agent might increase translation of mRNA to produce specific proteins. The ability of CAM to increase TRX production may account, at least in part, for the clinical efficacy of this agent on chronic airway inflammatory diseases, including chronic rhinosinositis.
authors.affiliation: Division of Physiology, School of Nursing and Rehabilitation Sciences, Showa University, 1865 Touka-Ichiba, Midori-ku, Yokohama, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Suzaki
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Asano
authors.forename: Ayako
authors.initials: A
authors.lastname: Kanei
authors.forename: Harumi
authors.initials: H
authors.lastname: Suzaki
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017291:Clarithromycin / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D013879:Thioredoxins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D017291:Clarithromycin