Organic cation transporter 1/2 (OCTN1/2) play important roles in the transport of drugs related to pulmonary inflammatory diseases. Nevertheless, the involvement of inflammation induced by cigarette smoke extract (CSE) combined with lipopolysaccharide (LPS) in the regulation of OCTN1/2 is not fully understood. In this study, CSE combined with LPS was used to establish inflammation models in vitro and in vivo. Our study found that the expression of OCTN1/2 was downregulated in rat lung in vivo and in a human alveolar cell line in vitro after treatment with CSE and LPS compared with the control group, while the expression of inflammatory factors was upregulated. After treatment with ipratropium bromide (IB) or dexamethasone (DEX), the expression of OCTN1/2 was upregulated compared with that in the CSE-LPS model group, while the expression of inflammatory factors was significantly downregulated. After administration of the NF-κB inhibitor PDTC on the basis of the inflammatory status, the expression of OCTN1/2 was upregulated in the treated group compared with the CSE-LPS model group, while the expression of phospho-p65, phospho-IκBα and inflammatory factors was significantly downregulated. We further added the NF-κB agonist HSP70 and found a result that the exact opposite of that observed with PDTC. Our findings show that CSE combined with LPS can downregulate the expression of OCTN1/2 under inflammatory conditions, and that the downregulation of OCTN1/2 expression may partially occur via the NF-κB signaling pathway.

有机阳离子转运蛋白1/2（OCTN1 / 2）在与肺炎性疾病有关的药物转运中起着重要作用。然而，尚不完全了解香烟烟雾提取物（CSE）结合脂多糖（LPS）引起的炎症与OCTN1 / 2的调控有关。在这项研究中，CSE与LPS的结合被用于建立体外和体内炎症模型。我们的研究发现，与对照组相比，CSE和LPS治疗后，大鼠体内肺和人肺泡细胞系中OCTN1 / 2的表达下调，而炎症因子的表达上调。与CSE-LPS模型组相比，异丙托溴铵（IB）或地塞米松（DEX）处理后，OCTN1 / 2的表达上调，而炎症因子的表达明显下调。根据炎症状态给予NF-κB抑制剂PDTC后，与CSE-LPS模型组相比，治疗组OCTN1 / 2的表达上调，而磷酸化p65，磷酸化IκBα和磷酸化p65的表达则升高。炎症因子明显下调。我们进一步添加了NF-κB激动剂HSP70，发现与PDTC观察到的结果完全相反。我们的研究结果表明，CSE与LPS结合可以在炎症条件下下调OCTN1 / 2的表达，而OCTN1 / 2表达的下调可能部分通过NF-κB信号通路发生。与CSE-LPS模型组相比，治疗组的OCTN1 / 2表达上调，而磷酸化p65，磷酸化IκBα和炎性因子的表达明显下调。我们进一步添加了NF-κB激动剂HSP70，发现与PDTC观察到的结果完全相反。我们的研究结果表明，CSE与LPS结合可以在炎症条件下下调OCTN1 / 2的表达，而OCTN1 / 2表达的下调可能部分通过NF-κB信号通路发生。与CSE-LPS模型组相比，治疗组的OCTN1 / 2表达上调，而磷酸化p65，磷酸化IκBα和炎性因子的表达明显下调。我们进一步添加了NF-κB激动剂HSP70，发现与PDTC观察到的结果完全相反。我们的研究结果表明，CSE与LPS结合可以在炎症条件下下调OCTN1 / 2的表达，而OCTN1 / 2表达的下调可能部分通过NF-κB信号通路发生。