Effect of cigarette smoke extract on P-glycoprotein function in primary cultured and newly developed alveolar epithelial cells

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• 作者：Mikihisa Takano ; ^{takanom@hiroshima-u.ac.jp} ; Ryosuke Naka ; Yoshihiro Sasaki ; Saori Nishimoto ; Ryoko Yumoto
• 关键词：Cigarette smoke extract ; Alveolar epithelial cells ; Transdifferentiation ; P-glycoprotein ; Rhodamine 123
• 刊名：Drug Metabolism and Pharmacokinetics
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：31
• 期：6
• 页码：417-424
• 全文大小：1302 K
• 卷排序：31

文摘

The effect of cigarette smoke extract (CSE) on P-glycoprotein (P-gp) function in the distal lung is unclear. In this study, we first examined the expression and function of P-gp and the effect of CSE in rat primary cultured alveolar epithelial cells. The expression of P-gp protein was observed in type I-like cells, but not in type II cells. In type I-like cells, rhodamine 123 (Rho123) accumulation was enhanced by various P-gp inhibitors such as verapamil and cyclosporine A. In addition, the expression of P-gp mRNAs, mdr1a and mdr1b, as well as P-gp activity increased along with the transdifferentiation. When type I-like cells were co-incubated with CSE, P-gp activity was suppressed. Next, we attempted to clarify the effect of CSE on P-gp function in human-derived cultured alveolar epithelial cells. For this purpose, we isolated an A549 clone (A549/P-gp) expressing P-gp, because P-gp expression in native A549 cells was negligible. In A549/P-gp cells, P-gp was functionally expressed, and the inhibitory effect of CSE on P-gp was observed. These results suggested that smoking would directly suppress P-gp activity, and that A549/P-gp cell line should be a useful model to further study the effect of xenobiotics on P-gp function in the alveolar epithelial cells.