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Suppression of Inducible Nitric Oxide Synthase Expression and Nitric Oxide Production by Macrolide Antibiotics in Sulfur Mustard‐Exposed Airway Epithelial Cells
Author(s) -
Gao Xiugong,
Ray Radharaman,
Xiao Yan,
Ray Prabhati
Publication year - 2008
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2008.00255.x
Subject(s) - nitric oxide , sulfur mustard , nitric oxide synthase , roxithromycin , microbiology and biotechnology , pharmacology , antibiotics , chemistry , inflammation , biochemistry , biology , immunology , toxicity , erythromycin , organic chemistry
Sulfur mustard, a vesicant chemical warfare agent, causes airway injury due to massive release of destructive enzymes and mediators of inflammation. Nitric oxide plays an important yet controversial role in inflammation. An impressive number of reports suggest that excessive amount of nitric oxide may promote inflammation‐induced cell injury and death. Overproduction of nitric oxide is catalysed by up‐regulated expression of the inducible isoform of nitric oxide synthase (iNOS). In this study, we used quantum dot‐mediated immunocytochemistry to analyse iNOS expression and flow cytometry to analyse the intracellular nitric oxide production in sulfur mustard‐exposed normal human small airway epithelial cells and bronchial/tracheal epithelial cells and studied the effect of four US Food and Drug Administration‐approved macrolide antibiotics, namely, azithromycin, clarithromycin, erythromycin and roxithromycin. Exposure to 100 µM sulfur mustard significantly up‐regulated iNOS expression and resulted in overproduction of nitric oxide in these cells. Addition of macrolide antibiotics to 100 µM in the medium reduced both iNOS expression and nitric oxide production to near normal level. Thus, the current study provides in vitro evidence of the immunomodulatory effects of macrolide antibiotics in sulfur mustard‐exposed airway epithelial cells. These results suggest that macrolide antibiotics may serve as potential vesicant respiratory therapeutics through mechanisms independent of their antibacterial activity.