Anti-Cytotoxic and Anti-Inflammatory Effects of the Macrolide Antibiotic Roxithromycin in Sulfur Mustard-Exposed Human Airway Epithelial Cells; Conference paper

摘要

Inhalation of sulfur mustard (SM) causes airway inflammation and injury. There is increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE) cells and bronchial/tracheal epithelial (BTE) cells. Cells were exposed to varying concentrations of SM with or without roxithromycin. Cytotoxicity was measured with the MTS assay and Calcein AM/ethidium homodimer (EthD-1) fluorescence staining. Cytokine protein expression was analyzed by enzyme-linked immunosorbent assay (ELISA) and cytokine mRNA expression by real-time RT-PCR. Inducible nitric oxide synthase (iNOS) protein expression was examined by a new immunocytochemical method using quantum dots as the fluorophore. Our results show that roxithromycin decreased SM cytotoxicity in both SAE and BTE cells. Also, roxithromycin inhibited the SM- stimulated overproduction of the proinflammatory cytokines interleukin (IL)-1 Beta, IL-6, IL-8 and TNF at both the mRNA level and the protein level. In addition, roxithromycin inhibited the SM-induced overexpression of iNOS. In conclusion, the present study demonstrates that roxithromycin has anti- cytotoxic and anti-inflammatory activities in human airway epithelial cells that likely depend on the ability of roxithromycin to down-regulate the production of proinflammatory mediators and cytokines, and suggests that macrolide antibiotics may serve as potential vesicant respiratory therapeutics through mechanisms independent of their antibacterial activity.