Department of Anatomy, Third Military Medical University, Chongqing, China.
Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing, China.
J Cell Physiol. 2019 Jun;234(6):8788-8796. doi: 10.1002/jcp.27537. Epub 2018 Oct 14.
The in vitro and in vivo effects of physalin D on macrophage M1/M2 polarization were investigated. In silico analysis was first performed for biological function prediction of different physalins. The results suggest physalins have similar predicted biological functions due to their similarities in chemical structures. The cytotoxicity of physalins was then analyzed based on cell apoptosis rate and cell viability evaluation. Physalin D was chosen for further study due to its minimal cytotoxicity. Bone marrow macrophages were isolated and induced with lipopolysaccharide/interferon (IFN)-γ for M1 polarization and interleukin (IL)-4/IL-13 for M2 polarization. The results showed that physalin D can repolarize M1 phenotype cells toward M2 phenotype. In addition, physalin D is protective in M2 macrophages to maintain the M2 phenotype in the presence of IFN-γ. On the molecular level, we found that physalin D suppressed the signal transducers and activators of transcription (STAT)1 activation and blocked STAT1 nuclear translocation. Conversely, physalin D can also activate STAT6 and enhance STAT6 nuclear translocation for M2 polarization. Taken together, these results suggested that physalin D regulates macrophage M1/M2 polarization via the STAT1/6 pathway.
研究了石蒜宁 D 在体外和体内对巨噬细胞 M1/M2 极化的影响。首先对不同石蒜宁的生物学功能进行了计算机分析预测。结果表明，由于化学结构相似，石蒜宁具有相似的预测生物学功能。然后基于细胞凋亡率和细胞活力评估分析了石蒜宁的细胞毒性。由于石蒜宁 D 的细胞毒性最小，因此选择其进行进一步研究。分离骨髓巨噬细胞并用脂多糖/干扰素 (IFN)-γ诱导 M1 极化，用白细胞介素 (IL)-4/IL-13 诱导 M2 极化。结果表明，石蒜宁 D 可以将 M1 表型细胞重新极化向 M2 表型。此外，石蒜宁 D 在存在 IFN-γ的情况下对 M2 巨噬细胞具有保护作用，以维持 M2 表型。在分子水平上，我们发现石蒜宁 D 抑制信号转导和转录激活因子 (STAT)1 激活并阻断 STAT1 核转位。相反，石蒜宁 D 还可以激活 STAT6 并增强 STAT6 核转位以促进 M2 极化。综上所述，这些结果表明石蒜宁 D 通过 STAT1/6 通路调节巨噬细胞 M1/M2 极化。
