Gene expression profiles of human small airway epithelial cells treated with low doses of 14- and 16-membered macrolides.
Although long-term treatment with low doses of 14-membered macrolides is widely applied in management of patients with chronic inflammatory diseases, e.g., diffuse panbronchiolitis, chronic bronchitis, or chronic lung damage in newborns, the physiological mechanisms underlying the action of macrolides in these conditions are unclear. To clarify the pathological basis of these diseases and also to aid in the design of novel drugs to treat them, we chose to investigate the molecular target(s) of macrolides. Our experiments involved long-term culture of human small airway epithelial cells (hSAEC) in media containing 14-membered macrolides erythromycin (EM) or clarithromycin (CAM), or a 16-membered macrolide, josamycin (JM), which lacks clinical anti-inflammatory effects. We then analyzed gene expression profiles in the treated cells using a cDNA microarray consisting of 18,432 genes. We identified nine genes whose expression was significantly altered during 22 days of culture with EM, and seven that were altered by CAM in that time. Four of those genes revealed similar behavior in cells treated with either of the 14-membered macrolides, but not JM. The products of these four genes may be candidates for mediating the ability of 14-membered macrolides to suppress chronic inflammation.
Yamanaka
Y
Y
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Tamari
M
M
Nakahata
T
T
Nakamura
Y
Y
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D017291:Clarithromycin / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology; D004917:Erythromycin / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D015570:Josamycin / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis
D000900:Anti-Bacterial Agents; D004917:Erythromycin; D017291:Clarithromycin; D015570:Josamycin