Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
PLoS One. 2013 May 9;8(5):e63845. doi: 10.1371/journal.pone.0063845. Print 2013.
Upregulation of intercellular adhesion molecule-1 (ICAM-1) involves adhesions between both circulating and resident leukocytes and the human lung epithelial cells during lung inflammatory reactions. We have previously demonstrated that curcumin-loaded polyvinylpyrrolidone nanoparticles (CURN) improve the anti-inflammatory and anti-oxidative properties of curcumin in hepatocytes. In this study, we focused on the effects of CURN on the expression of ICAM-1 in TNF-α-treated lung epithelial cells and compared these to the effects of curcumin water preparation (CURH). TNF-αinduced ICAM-1 expression, ROS production, and cell-cell adhesion were significantly attenuated by the pretreatment with antioxidants (DPI, APO, or NAC) and CURN, but not by CURH, as revealed by western blot analysis, RT-PCR, promoter assay, and ROS detection and adhesion assay. In addition, treatment of TNF-α-treated cells with CURN and antioxidants also resulted in an inhibition of activation of p47 (phox) and phosphorylation of MAPKs, as compared to that using CURH. Our findings also suggest that phosphorylation of MAPKs may eventually lead to the activation of transcription factors. We also observed that the effects of TNF-α treatment for 30 min, which includes a significant increase in the binding activity of AP-1 and phosphorylation of c-jun and c-fos genes, were reduced by CURN treatment. In vivo studies have revealed that CURN improved the anti-inflammation activities of CURH in the lung epithelial cells of TNF-α-treated mice. Our results indicate that curcumin-loaded polyvinylpyrrolidone nanoparticles may potentially serve as an anti-inflammatory drug for the treatment of respiratory diseases.
细胞间黏附分子-1（ICAM-1）的上调涉及循环和驻留白细胞与肺上皮细胞之间的黏附，发生于肺部炎症反应过程中。我们先前的研究已经证实，负载姜黄素的聚乙烯吡咯烷酮纳米粒（CURN）可提高姜黄素在肝细胞中的抗炎和抗氧化作用。在这项研究中，我们关注 CURN 对 TNF-α处理的肺上皮细胞中 ICAM-1表达的影响，并将其与姜黄素水制剂（CURH）的作用进行比较。Western blot 分析、RT-PCR、启动子测定、ROS 检测和细胞黏附测定显示，TNF-α诱导的 ICAM-1表达、ROS 产生和细胞间黏附，经抗氧化剂（DPI、APO 或 NAC）和 CURN 预处理后显著减弱，但 CURH 则无此作用。此外，与使用 CURH 相比，用 CURN 和抗氧化剂处理 TNF-α处理的细胞也可抑制 p47（phox）的激活和 MAPKs 的磷酸化。我们的研究结果还表明，MAPKs 的磷酸化最终可能导致转录因子的激活。我们还观察到，TNF-α处理 30 分钟后，AP-1 的结合活性和 c-jun 和 c-fos 基因的磷酸化显著增加，CURN 处理可减少 TNF-α的这种作用。体内研究表明，CURN 可提高 CURH 在 TNF-α处理的小鼠肺上皮细胞中的抗炎活性。我们的研究结果表明，负载姜黄素的聚乙烯吡咯烷酮纳米粒可能可作为一种治疗呼吸道疾病的抗炎药物。
