Cigarette smoking is the principal cause of chronic obstructive lung disease (COPD), especially emphysema, which is characterized by alveolar wall destruction and airspace enlargement. Apoptosis of lung structural cells is involved in the pathogenesis of COPD. Xanthine derivatives (aminophylline or theophylline) have been used for the treatment of COPD as a bronchodilator. But, the effects of xanthine derivatives on apoptosis of the lung structural cells remains poorly understood, even though it is known that theophylline protects against ultraviolet irradiation-induced cell death in corneal epithelial cells. This study was designed to determine whether aminophylline would protect against cigarette smoke extract (CSE)-induced apoptosis in lung fibroblasts.
We demonstrated that aminophylline protected against apoptosis of MRC-5 cells at a relatively lower therapeutic range (10 ug/ml), resulting in a significant increase in cell viability occurring at 20% concentration after 8 hr exposure. Annexin staining decreased from 68 ± 4% of the control to 12 ± 2% of aminophylline (10 ug/ml) pre-treatment after 20% CSE exposure for 12 hr (p<0.05). Aminophylline decreased caspase 3 and 8 activity and nuclear condensation or fragmentation in MRC-5 cells after exposing 20% CSE for 12 hr compared with control and high levels of aminophylline (> 50 ug/ml) pre-treatment. These findings suggest that aminophylline protected against apoptosis of MRC-5 cells through the inactivation of caspase 3 and 8, and could be an effective agent to reduce cigarette smoking-induced lung structural cell apoptosis.
Authors: Kim YJ, Kim JY, Yoon JY, Kyung SY, Lee SP, Jeong SH, Moon C, Park JW
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