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Protective Effect of Aminophylline against Cigarette Smoke Extract–Induced Apoptosis in Human Lung Fibroblasts (MRC‐5 Cells)
Author(s) -
Kim Yu J.,
Kim JuYoung,
Yoon Jin Y.,
Kyung Sun Y.,
Lee Sang P.,
Jeong Sung H.,
Moon Chanil,
Park JeongWoong
Publication year - 2011
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.1742-7843.2011.00673.x
Subject(s) - aminophylline , apoptosis , cigarette smoke , pharmacology , human lung , smoke , medicine , lung , chemistry , cancer research , toxicology , biology , biochemistry , organic chemistry
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 < 0.05). Aminophylline decreased caspase 3 and 8 activities and nuclear condensation or fragmentation in MRC‐5 cells after exposure to 20% CSE for 12 hr compared with control and high levels of aminophylline (>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.