The Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
Department of Immunology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Oxid Med Cell Longev. 2021 Jun 17;2021:5527935. doi: 10.1155/2021/5527935. eCollection 2021.
Inflammatory bowel diseases (IBD) are prevalent and debilitating diseases; their clinical remedy is desperately unmet. Mesenchymal stem cells (MSCs) are pluripotent stem cells with multiple immunomodulatory effects, which are attributed to their efficacy in the IBD rodent model. Optimization of MSC regimes in IBD is a crucial step for their further clinical application. Wogonin is a flavonoid-like compound, which showed extensive immunomodulatory and adjuvant effects. This research is aimed at investigating whether and how Wogonin boosted the therapeutic efficiency of MSCs on DSS-induced colitis. Our results showed that the MSC treatment with Wogonin significantly alleviated the intestinal inflammation in IBD mice by increased IL-10 expression. In vitro experiments, Wogonin obviously raised the IL-10 production and ROS levels of MSCs in a dose-dependent manner. Meanwhile, western blot data suggested Wogonin improves the IL-10 production by inducing transcript factor HIF-1 expression via AKT/GSK3 signal pathway. Finally, the favorable effects of Wogonin on MSCs were confirmed by IL-10 blockade experiment in vivo. Together, our results suggested that Wogonin significantly increased the IL-10 production and enhanced the therapeutic effects of MSCs in DSS-induced colitis. This work suggested Wogonin as a novel optimal strategy for MSC clinical application.
炎症性肠病(IBD)是一种普遍且使人虚弱的疾病;其临床治疗方法仍严重不足。间充质干细胞(MSCs)是一种多能干细胞,具有多种免疫调节作用,这归因于其在 IBD 啮齿动物模型中的疗效。优化 IBD 中的 MSC 方案是其进一步临床应用的关键步骤。白杨素是一种类黄酮化合物,具有广泛的免疫调节和佐剂作用。本研究旨在探讨白杨素是否以及如何增强 MSCs 对 DSS 诱导的结肠炎的治疗效果。我们的结果表明,用白杨素处理的 MSC 可通过增加 IL-10 表达显著减轻 IBD 小鼠的肠道炎症。在体外实验中,白杨素以剂量依赖性方式明显提高了 MSC 的 IL-10 产生和 ROS 水平。同时,Western blot 数据表明,白杨素通过 AKT/GSK3 信号通路诱导转录因子 HIF-1 的表达来改善 IL-10 的产生。最后,体内的 IL-10 阻断实验证实了白杨素对 MSCs 的有利影响。总之,我们的研究结果表明,白杨素显著增加了 MSC 的 IL-10 产生,并增强了 MSCs 在 DSS 诱导的结肠炎中的治疗效果。这项工作表明,白杨素是 MSC 临床应用的一种新的最佳策略。