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The transporter multidrug resistance protein 2 (MRP2) can transport some tobacco carcinogens and plays an important role in the transport of mediators related to pulmonary inflammatory diseases. However, it is not fully understood whether the pulmonary inflammation caused by cigarette smoke extract (CSE) and lipopolysaccharide (LPS) is related to the regulation of MRP2. In this study, CSE and LPS were used alone and in combination as stimuli to induce pulmonary inflammation. In addition, the establishment of a pulmonary inflammation model was verified by animal experiments in vivo. We found that compared with those in the control group, the expression of MRP2 protein was downregulated and the expression of inflammatory cytokines was upregulated in pulmonary inflammation in the CSE group and the CSE combined with LPS group. However, there was almost no change in the expression of MRP2 stimulated by LPS alone. Our results show that CSE and CSE combined with LPS downregulate the expression of MRP2 under inflammatory conditions, while LPS has almost no effect on the expression of MRP2 under inflammatory conditions. The in vivo experimental results of CSE combined with LPS were consistent with the cellular results of CSE combined with LPS, which provides a model and basis for other studies of the role of MRP2 in pulmonary inflammation.

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 ( K m ) and apparent permeability coefficient (P app ) 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.