title: Protective effect of aminophylline against cigarette smoke extract-induced apoptosis in human lung fibroblasts (MRC-5 cells).
abstract: 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.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Gachon University Gil Hospital, Incheon, Korea.
authors.forename: Yu J
authors.initials: YJ
authors.lastname: Kim
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jin Y
authors.initials: JY
authors.lastname: Yoon
authors.forename: Sun Y
authors.initials: SY
authors.lastname: Kyung
authors.forename: Sang P
authors.initials: SP
authors.lastname: Lee
authors.forename: Sung H
authors.initials: SH
authors.lastname: Jeong
authors.forename: Chanil
authors.initials: C
authors.lastname: Moon
authors.forename: Jeong-Woong
authors.initials: JW
authors.lastname: Park
mesh_terms: D000628:Aminophylline / Q000008:administration & dosage / Q000494:pharmacology*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D053181:Caspase 8 / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D013194:Staining and Labeling; D014026:Nicotiana / Q000737:chemistry / Q000633:toxicity*
chemical_list: D017304:Annexin A5; D001993:Bronchodilator Agents; D012906:Smoke; D000628:Aminophylline; D053148:Caspase 3; D053181:Caspase 8