The Effect of Cordycepin and Simvastatin on Cigarettes Smoke Extract Induced Cytokine and Chemokine Production in Human Bronchial Epithelial Cells

COPD is a common chronic inflammatory lung disease with cigarette smoke (CS) as the major cause. The receptor for advanced glycation end products (RAGE) and its ligands are critically involved in inflammation. Inhaled corticosteroids are poorly effective in improving the symptoms of COPD. This underlines the need for new anti-inflammatory therapies. Cordycepin is a purine nucleoside antimetabolite. Simvastatin is a lipid-lowering agent. But the effect of Cordycepin and Simvastatin on CSE-induced inflammatory gene expression in human bronchial epithelial cells has not been explored. Human BEAS-2B bronchial epithelial cells were treated with Cordycepin + CSE (2.5%) and Simvastatin + CSE (2.5%). IL-8 andIL-6 production was measured by ELISA. RAGE and RAGE ligand HMBG-1 expression was analysed by Western blot. We found that CSE-induced IL-8 production was inhibited by Cordycepin and Simvastatin but IL-6 production was enhanced by Cordycepin and not affected by Simvastatin. CSE and both drugs had no effect on basal RAGE and HMGB-1 expression. Since IL-6 contribute to the pathogenesis of COPD by modulating pulmonary function but not necessarily inflammation and neutrophil-driven airway inflammation (by IL-8 and other chemokines) is critically involved in the pathogenesis of COPD, our findings suggest cigarette smoke, by inducing inflammatory responses from human bronchial epithelial cells, may play an important role in airway inflammation in COPD and that Cordycepin and Simvastatin, by reducing IL-8 production (unlikely via RAGE inhibition), may have therapeutic potential in COPD.