College of Pharmacy, Sunchon National University, 255 Jungangno, Suncheon 540-950, Korea.
Int J Mol Sci. 2020 Mar 4;21(5):1753. doi: 10.3390/ijms21051753.
In addition to their use as colorants, anthraquinone derivatives have numerous medical applications, for example, as antibacterial and antiinflammatory agents. We confirmed that physcion (an anthraquinone derivative) induces TNF-alpha production by macrophages and increased the expressions of surface molecules (CD40, CD80, and CD86) and major histocompatibility complex (MHC) II. Based on these results, we hypothesized that physcion might induce the maturation of dendritic cells (DCs) to antigen-presenting cells (APCs), and decided to conduct in vitro experiments using bone-marrow-derived DCs (BMDCs). Physcion was not toxic to DCs and increased the expression of surface molecules (e.g., CD40, CD80, CD86, and MHC II) and the production of cytokines (e.g., IL-12p70, IL-1beta, IL-6, and TNF-alpha), but not of IL-10. To confirm that DCs matured by physcion induce T-cell-immune responses, naive CD4 T cells were treated with physcion-treated DCs or their supernatants. Physcion induced the maturation of DCs, which promoted the polarization of Th1 cells. Our results show physcion-induced DC maturation via TLR4, and that mature DCs promote the differentiation of Th1 cells without affecting the differentiation of Th2 cells. These findings show that physcion has potential use as a treatment for inflammatory diseases associated with Th1/Th2 cell imbalance.
除了作为着色剂,蒽醌衍生物在医学上也有广泛的应用,例如作为抗菌和抗炎药物。我们证实大黄素(一种蒽醌衍生物)可诱导巨噬细胞产生 TNF-α,并增加表面分子(CD40、CD80 和 CD86)和主要组织相容性复合体(MHC)II 的表达。基于这些结果,我们假设大黄素可能诱导树突状细胞(DC)向抗原呈递细胞(APC)成熟,并决定使用骨髓来源的树突状细胞(BMDC)进行体外实验。大黄素对 DC 没有毒性,并且增加了表面分子(例如 CD40、CD80、CD86 和 MHC II)的表达和细胞因子(例如 IL-12p70、IL-1β、IL-6 和 TNF-α)的产生,但不产生 IL-10。为了证实大黄素成熟的 DC 可诱导 T 细胞免疫反应,我们用大黄素处理的 DC 或其上清液处理幼稚 CD4 T 细胞。大黄素诱导 DC 成熟,促进 Th1 细胞的极化。我们的结果表明,大黄素通过 TLR4 诱导 DC 成熟,成熟的 DC 促进 Th1 细胞的分化,而不影响 Th2 细胞的分化。这些发现表明,大黄素有潜力用作治疗与 Th1/Th2 细胞失衡相关的炎症性疾病的药物。