泽漆汤通过下调 p21/Hif1α/Glut1 信号抑制银屑病样小鼠 MDSCs 的糖酵解。
Ze-Qi-Tang formula inhibits MDSCs glycolysis through the down-regulation of p21/Hif1α/Glut1 signal in psoriatic-like mice.
机构信息
Shanghai Key Laboratory of Health Identification and Assessment, School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd., Pudong District, Shanghai, 201203, China.
Department of Traditional Chinese Medicine Dermatology, Shanghai Skin Disease Hospital, 1278 Baode Rd., Jingan District, Shanghai, 200443, China.
出版信息
Phytomedicine. 2024 Jul 25;130:155544. doi: 10.1016/j.phymed.2024.155544. Epub 2024 Mar 26.
BACKGROUND
Psoriasis is a chronic immune-mediated inflammatory skin disease that affects the quality of life and mental health of approximately 150 million people worldwide. Ze-Qi-Tang (ZQT) is a classic compound used in China for lung disease; however, its mechanism of action in psoriasis remains unclear. This study aimed to investigate the therapeutic effect of the ZQT formula on psoriasis and explore the underlying molecular mechanisms.
METHODS
Peripheral blood samples were collected from patients with psoriasis and healthy individuals. Flow cytometry was used to detect changes in the proportions of myeloid-derived suppressor cells (MDSCs) and other immune cells. Psoriasis was induced in mice by the daily application of imiquimod. ZQT was administered separately or in combination with anti-Gr1 antibody to deplete MDSC. The glycolysis levels of the MDSCs were detected using a Seahorse analyzer. The p21/Hif1α/Glut1 pathway was identified and validated by mRNA sequence, RT-qPCR, WB, IF, and the application of p21 inhibitor UC2288.
RESULTS
The number of MDSCs was significantly increased in patients with psoriasis, with the increased expression of p21, Hif1α, and Glut1 in MDSCs. ZQT significantly alleviated psoriasis-like skin lesions in mice. ZQT formula significantly reduced the number of MDSCs in psoriatic-like mice and enhanced their suppressive capacity for T cells. The efficacy of ZQT in alleviating psoriatic dermatitis is compromised by MDSC depletion. ZQT decreased the expressions of p21, Hif1α, and Glut1-induced glycolysis in MDSCs, thereby inhibiting Th17 cell differentiation.
CONCLUSION
These suggest that ZQT alleviates IMQ-induced psoriatic dermatitis, by inhibiting p21/Hif1α/Glut1-induced glycolysis in MDSCs.
背景
银屑病是一种慢性免疫介导的炎症性皮肤病，影响着全球约 1.5 亿人的生活质量和心理健康。泽七汤（ZQT）是一种经典的复方中药，用于治疗肺部疾病；然而，其在银屑病中的作用机制尚不清楚。本研究旨在探讨 ZQT 配方治疗银屑病的疗效，并探讨其潜在的分子机制。
方法
收集银屑病患者和健康个体的外周血样本。流式细胞术检测髓系来源抑制细胞（MDSCs）和其他免疫细胞比例的变化。采用咪喹莫特诱导小鼠银屑病模型。分别给予 ZQT 或联合抗-Gr1 抗体以耗竭 MDSC。使用 Seahorse 分析仪检测 MDSC 的糖酵解水平。通过 mRNA 序列、RT-qPCR、WB、IF 和 p21 抑制剂 UC2288 的应用，鉴定和验证 p21/Hif1α/Glut1 通路。
结果
银屑病患者 MDSC 数量明显增加，MDSC 中 p21、Hif1α 和 Glut1 的表达增加。ZQT 显著缓解了小鼠的银屑病样皮肤损伤。ZQT 配方显著减少了银屑病样小鼠中 MDSC 的数量，并增强了其对 T 细胞的抑制作用。MDSC 耗竭削弱了 ZQT 缓解银屑病样皮炎的疗效。ZQT 降低了 MDSC 中 p21、Hif1α 和 Glut1 诱导的糖酵解表达，从而抑制了 Th17 细胞分化。
结论
这些结果表明，ZQT 通过抑制 MDSC 中 p21/Hif1α/Glut1 诱导的糖酵解，缓解了 IMQ 诱导的银屑病样皮炎。
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