结肠炎
炎症性肠病
雷公藤甲素
免疫学
T辅助细胞
斯达
细胞分化
医学
信号转导
T细胞
癌症研究
生物
免疫系统
细胞生物学
内科学
车站3
疾病
细胞凋亡
基因
生物化学
作者
Junmin Fu,Yingda Zang,Yu Zhou,Chengjuan Chen,Shuai Shao,Gaona Shi,Lei Wu,Guo‐Yuan Zhu,Tao Sun,Dongming Zhang,Tiantai Zhang
标识
DOI:10.1016/j.intimp.2021.107472
摘要
Inflammatory bowel disease (IBD) is generally characterized by chronic inflammatory disorders of the gastrointestinal tract that are known as ulcerative colitis (UC) or Crohn’s disease (CD). Although the underlying mechanism of action of IBD is unclear and because of the lack of satisfactory treatment, increasing evidence has indicated that pro-inflammatory cytokines that activate JAK-STAT signaling pathway regulate the differentiation of naïve T cells towards T helper (Th)1 and Th17 cell subsets and contribute to the development of IBD. ZT01 is a newly obtained triptolide derivative with strong anti-inflammatory effects and low toxicity. In this study, we evaluated the effects of ZT01 on DSS-induced colitis and investigated the underlying mechanism of action involved. Mice with DSS-induced acute or chronic colitis were used to assess the efficacy of ZT01 treatment, and T cells were cultured to analyze the differentiation of Th1 and Th17 cell by flow cytometry. In addition, intestinal epithelial barrier function, macrophage polarization, activation of the JAK-STAT signaling pathway, and the expression of cytokines and transcription factors were measured to assess the possible mechanisms of ZT01. We found that ZT01 had an obviously beneficial effect on DSS-induced colitis by improving the symptoms of bloody diarrhea, weight loss, and a shortened colon, thereby preserving the epithelial barrier function in the mouse colon. Furthermore, ZT01 significantly inhibited T cell differentiation into Th1 and/or Th17 cell subsets and macrophage polarization towards into an inflammatory phenotype via regulating the JAK-STAT signaling pathway. Thus, our findings suggested that ZT01 might be a potential pharmaceutical candidate that deserves to be further investigated as a treatment for IBD patients.
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