药物筛选发现吡咯烷二硫代氨基甲酸铵可通过抑制 Th17 分化改善 DSS 诱导的小鼠溃疡性结肠炎

IF 3.7 4区医学 Q2 CELL BIOLOGY

Cellular immunology Pub Date : 2024-10-22 DOI:10.1016/j.cellimm.2024.104887

Yu-e Guo , Jie Lv , Ping Shu , Xi Li , Ying Li , Junhong Guo , Guofang Chen , Yuping Li , Bo Lu , Wei Zhang , Yin Liu

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引用次数: 0

摘要

T 辅助细胞 17（Th17）在各种自身免疫性疾病中发挥着至关重要的作用，包括以结肠和直肠粘膜广泛炎症为特征的溃疡性结肠炎（UC）。为了找出能够抑制 CD4+ T 细胞分化成 Th17 细胞的小分子化合物，我们建立了一个筛选系统。通过药物筛选，我们发现吡咯烷二硫代氨基甲酸铵（PDTC）能有效抑制 Th17 分化。在右旋糖酐硫酸钠（DSS）诱导的 UC 小鼠模型中，服用 PDTC 能显著改善结肠炎。PDTC 通过抑制 NF-κB 激活，减少了促炎介质的产生，并抑制了结肠炎小鼠 Th17 细胞的比例。这些研究结果表明，PDTC 可通过抑制 NF-κB 激活来缓解结肠炎。在 UC 小鼠模型中观察到的 PDTC 治疗效果为其在临床中的应用提供了依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Drug screening identifies pyrrolidinedithiocarbamate ammonium ameliorating DSS-induced mouse ulcerative colitis via suppressing Th17 differentiation

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Drug screening identifies pyrrolidinedithiocarbamate ammonium ameliorating DSS-induced mouse ulcerative colitis via suppressing Th17 differentiation

T helper 17 (Th17) cells play crucial roles in various autoimmune diseases, including ulcerative colitis (UC), which is characterized by widespread inflammation in the mucosa of the colon and rectum. To identify small-molecule compounds capable of inhibiting CD4⁺ T cell differentiation into Th17 cells, we established a screening system. Through drug screening, we found that pyrrolidinedithiocarbamate ammonium (PDTC) effectively inhibits Th17 differentiation. In a dextran sulfate sodium (DSS)-induced UC mouse model, administration of PDTC significantly ameliorated colitis. PDTC treatment decreased the production of proinflammatory mediators and inhibited the proportion of Th17 cells in colitis-afflicted mice by suppressing NF-κB activation. These findings showed that PDTC can alleviate colitis by inhibiting NF-κB activation. The therapeutic effects of PDTC observed in a mouse model of UC provided a rationale for its application in clinical settings.

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来源期刊

Cellular immunology 生物-免疫学

CiteScore

8.20

自引率

2.30%

发文量

102

审稿时长

30 days

期刊介绍： Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.