哮喘联盟

   摘要
   香烟烟雾是慢性阻塞性肺病的主要致病因素，其诱导肺细胞死亡机制尚不明确。香烟烟雾导致的肺细胞凋亡是肺气肿的发病机理。在小鼠实验中，磷酸二酯酶-4抑制剂是用于治疗COPD的抗炎药物，可以预防因香烟烟雾引起的肺气肿。本研究旨在评价第一代PDE4抑制剂咯利普兰在调节香烟烟雾诱导的细胞凋亡中的作用。将人肺成纤维细胞暴露于香烟烟雾提取物中，分别用MTT比色法和膜联蛋白-v染色来确定细胞活性和细胞凋亡。半胱天冬酶活化由西方免疫印迹分析法来确定。结果显示，咯利普兰有效防止暴露于香烟烟雾的MRC-5成纤维细胞的凋亡，增加活力，并且可减少半胱天冬酶-3和半胱天冬酶-8的分裂。治疗前使用咯利普兰可提高暴露于CSE细胞的磷酸化，与细胞保护作用相关，可逆转P13K抑制剂LY294002。结论，咯利普兰通过抑制半光天冬酶-3和半光天冬酶-8来防止MRC-5细胞的凋亡。咯利普兰可成为减少由香烟烟雾诱导的肺成纤维细胞凋亡的有效药物。

                                                                 (林江涛 审校)
EurJPharmacol.2013Mar13.pii:S0014-2999(13)00158-1.doi:10.1016/j.ejphar.2013.02.049. [Epub ahead of print]
 

The phosphodiesterase 4 inhibitor rolipram protects against cigarette smokeextract-induced apoptosis in human lung fibroblasts.
 

Park JW, Ryter SW, Young Kyung S, Pyo Lee S, Hwan Jeong S.

Source
Department of Pulmonary and Critical Care Medicine, Gachon University, Gil Medical Center, 1198 Guwol Dong, Namdong-Gu, Incheon, Republic of Korea. Electronic address: jwpark@gilhospital.com.

Abstract
Cigarette smoke, a major causative agent of chronic obstructive pulmonary disease (COPD), induces lung cell death by incompletely understood mechanisms. The induction of apoptosis in lung structural cells by cigarette smoke may contribute to the pathogenesis of emphysema. Phosphodiesterase-4 (PDE4) inhibitors are anti-inflammatory agents used in COPD therapy that can prevent cigarette smoke-induced emphysema in mice. We investigated the effect of rolipram, a first generation PDE4 inhibitor, on the regulation of cigarette smoke-induced apoptosis. Human lung fibroblast (MRC-5) cells were exposed to cigarette smoke extract (CSE). Cell viability and apoptosis were determined by MTT assay and Annexin-V staining, respectively. Caspase activation was determined by Western immunoblot analysis. Rolipram protected against cell death and increased viability in MRC-5 fibroblasts after CSE exposure. Furthermore, rolipram protected against apoptosis, decreased caspase-3 and -8 cleavage in MRC-5 cells exposed to CSE. Pre-treatment with rolipram enhanced Akt phosphorylation and associated cytoprotection in CSE-treated cells, which could be reversed by the PI3K inhibitor LY294002 partly. In conclusion, rolipram protects against apoptosis of MRC-5 cells through inhibition of caspase-3 and caspase-8. Rolipram may represent an effective therapeutic agent to reduce cigarette smoke-induced apoptosis of lung fibroblasts.
 

Eur J Pharmacol. 2013 Mar 13. pii: S0014-2999(13)00158-1. doi: 10.1016/j.ejphar.2013.02.049. [Epub ahead of print]