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 wi dely 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 macrolid es in these conditions are unclear. To clarify the pathological basis of th ese 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 experiment s involved long-term culture of human small airway epithelial cells (hSAEC) in media containing 14-membered macrolides erythromycin (EM) or clarithrom ycin (CAM), or a 16-membered macrolide, josamycin (JM), which lacks clinica l anti-inflammatory effects. We then analyzed gene expression profiles in t he treated cells using a cDNA microarray consisting of 18,432 genes. We ide ntified nine genes whose expression was significantly altered during 22 day s 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 t he 14-membered macrolides, but not JM. The products of these four genes may be candidates for mediating the ability of 14-membered macrolides to suppr ess chronic inflammation. (C) 2001 Academic Press.