Cigarette smoke extract combined with lipopolysaccharide reduces OCTN1/2 expression in human alveolar epithelial cells in vitro and rat lung in vivo under inflammatory conditions.

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.