Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan.
Lung. 2012 Dec;190(6):651-9. doi: 10.1007/s00408-012-9413-9. Epub 2012 Sep 8.
The main purpose of this study was to evaluate the effect of cigarette smoke extract (CSE) on insulin transport in alveolar epithelial cells.
We first examined the effect of CSE pretreatment on cell viability, mRNA expression, and lamellar body structures in A549 cells. Then the effect of CSE pretreatment on FITC-insulin transport was examined.
When A549 cells were treated with 30 μg/ml of CSE for 48 h, the expression of some mRNAs abundantly expressed in type II alveolar epithelial cells such as surfactant protein B was significantly increased. Lamellar bodylike structures became more evident with CSE treatment. FITC-insulin uptake from the apical side and subsequent efflux to the basal side was enhanced by CSE treatment in A549 cells. The enhancing effect of CSE on FITC-insulin uptake was concentration-dependent and reversible. A concentration-dependent enhancing effect of CSE on FITC-insulin uptake was also observed in normal, primary cultured alveolar type II epithelial cells isolated from rats.
Treatment of A549 cells by CSE may direct the cells to a more type II-like phenotype. In accordance with this observation, FITC-insulin uptake was enhanced by CSE treatment. These results may partly explain the higher insulin absorption from the lung in smokers than in nonsmokers.
本研究的主要目的是评估香烟烟雾提取物(CSE)对肺泡上皮细胞胰岛素转运的影响。
我们首先研究了 CSE 预处理对 A549 细胞活力、mRNA 表达和板层小体结构的影响。然后,研究了 CSE 预处理对 FITC-胰岛素转运的影响。
当 A549 细胞用 30μg/ml 的 CSE 处理 48 小时时,一些在 II 型肺泡上皮细胞中大量表达的 mRNA 的表达,如表面活性蛋白 B,明显增加。用 CSE 处理后,板层小体样结构变得更加明显。CSE 处理增强了 FITC-胰岛素从顶端侧摄取并随后向基底侧流出。CSE 对 FITC-胰岛素摄取的增强作用呈浓度依赖性和可逆转性。在从大鼠分离的正常原代培养的 II 型肺泡上皮细胞中,也观察到 CSE 对 FITC-胰岛素摄取的浓度依赖性增强作用。
CSE 处理 A549 细胞可能使细胞向更类似于 II 型的表型发展。根据这一观察结果,CSE 处理增强了 FITC-胰岛素的摄取。这些结果部分解释了吸烟者肺部对胰岛素的吸收高于非吸烟者的原因。