Protective Effect of Aminophylline against Cigarette Smoke Extract–Induced Apoptosis in Human Lung Fibroblasts (MRC‐5 Cells)

• Published in: Basic & clinical pharmacology & toxicology 2011-07, Vol.109 (1), p.17-22
• Main Authors: Kim, Yu J., Kim, Ju‐Young, Yoon, Jin Y., Kyung, Sun Y., Lee, Sang P., Jeong, Sung H., Moon, Chanil, Park, Jeong‐Woong
• Format: Article
• Language: English
• Subjects: Alveoli; Aminophylline - administration & dosage; Aminophylline - pharmacology; Annexin A5 - metabolism; Annexins; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Bronchodilator Agents - administration & dosage; Bronchodilator Agents - pharmacology; Bronchodilators; Caspase 3 - drug effects; Caspase 3 - metabolism; Caspase 8 - drug effects; Caspase 8 - metabolism; Caspase-3; Cell Survival - drug effects; Cells, Cultured; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarette smoking; Condensation; Cornea; Dose-Response Relationship, Drug; Emphysema; Epithelial cells; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Humans; Lung - cytology; Lung - drug effects; Lung - metabolism; Medical sciences; Nicotiana - chemistry; Nicotiana - toxicity; Pharmacology. Drug treatments; Smoke - adverse effects; Staining and Labeling; Theophylline; Tobacco, tobacco smoking; Toxicology; U.V. radiation; Xanthine
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/j.1742-7843.2011.00673.x

:  Cigarette smoking is the principal cause of chronic obstructive pulmonary 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 remain 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 μg/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 μg/ml) pre‐treatment after 20% CSE exposure for 12 hr (p 50 μg/ml) pre‐treatment. These findings suggest that aminophylline protected apoptosis of MRC‐5 cells through the inactivation of caspases 3 and 8 and could be an effective agent to reduce cigarette smoking–induced lung structural cell apoptosis.