Organic cation transporters (OCTNs) can significantly affect drug disposition in alveolar epithelial cells (A549), but this process is not well understood. We investigated the expression and function of OCTN1/2 in A549 cells under different inflammatory status to examine pulmonary drug distribution. This experiment used lipopolysaccharide (LPS)-treated A549 cells to mimic inflammation in alveolar epithelial cells, and the expression of OCTN1/2, interleukin-6 (IL6), IL18, IL1β and tumour necrosis factor-alpha (TNF-α) was investigated by western blot and quantitative real-time PCR (qRT-PCR). The fluorescent compound 4-(4-(dimethylamino)styryl)-N-methylpyridinium iodide (ASP+) was chosen as a probe to study the activity of OCTN1/2. OCTN1/2 down-regulation induced by LPS was more pronounced than that in normal control (NC) groups. Experiments further detected the release of inflammatory factors that revealed a negative correlation between OCTN1/2 expression and inflammation secretion in human alveolar epithelial cells exposed to different concentrations of LPS. The Michaelis constant (Km) and apparent permeability coefficient (Papp) of ASP+ were also decreased significantly. Our results thus show that LPS-induced inflammation could inhibit the expression and activity of OCTN1/2 in vitro and reduce the distribution of inhaled medicine in pulmonary diseases.

中文翻译：

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由于肺泡上皮细胞中 OCTN1/2 的下调，LPS 诱导的炎症延迟了 ASP+ 的转运。

有机阳离子转运蛋白 (OCTN) 可以显着影响肺泡上皮细胞 (A549) 中的药物配置，但这一过程尚不清楚。我们研究了 OCTN1/2 在不同炎症状态下 A549 细胞中的表达和功能，以检查肺部药物分布。本实验使用脂多糖 (LPS) 处理的 A549 细胞模拟肺泡上皮细胞的炎症，并研究了 OCTN1/2、白细胞介素-6 (IL6)、IL18、IL1β 和肿瘤坏死因子-α (TNF-α) 的表达通过蛋白质印迹和实时定量 PCR (qRT-PCR)。选择荧光化合物 4-(4-(二甲氨基)苯乙烯基)-N-甲基吡啶碘化物 (ASP+) 作为探针来研究 OCTN1/2 的活性。LPS 诱导的 OCTN1/2 下调比正常对照 (NC) 组更明显。实验进一步检测了炎症因子的释放，揭示了暴露于不同浓度 LPS 的人肺泡上皮细胞中 OCTN1/2 表达与炎症分泌之间的负相关。ASP+的米氏常数（Km）和表观渗透系数（Papp）也显着降低。因此，我们的结果表明，LPS 诱导的炎症可以在体外抑制 OCTN1/2 的表达和活性，并减少吸入药物在肺部疾病中的分布。ASP+的米氏常数（Km）和表观渗透系数（Papp）也显着降低。因此，我们的结果表明，LPS 诱导的炎症可以在体外抑制 OCTN1/2 的表达和活性，并减少吸入药物在肺部疾病中的分布。ASP+的米氏常数（Km）和表观渗透系数（Papp）也显着降低。因此，我们的结果表明，LPS 诱导的炎症可以在体外抑制 OCTN1/2 的表达和活性，并减少吸入药物在肺部疾病中的分布。