通过ptolide 干预与结性脊髓炎相关的炎症,促进组织蛋白 H3 Iys-27 三甲基化
Xiao-Han Xu1, Jin-Xu Zhang2, Hong-Xiao Liu1
1Department of Rheumatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing China.
托利德 (TP) 通过上调H3K27me3.3,抑制结性脊髓炎 (AS) 中的Th17细胞分化. 这项研究支持TP.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 类风湿病学 类风湿病学
背景情况:
- Th17细胞在结性脊柱炎 (AS) 的发病过程中起着至关重要的作用.
- 了解调节Th17细胞分化的分子机制对于开发针对AS的向疗法至关重要.
研究的目的:
- 为了研究Triptolide (TP) 对Th17细胞分化在患有活跃结性脊髓炎 (AS) 的患者的影响.
- 阐明潜在的分子机制,包括JAK2/STAT3信号通路和表观遗传修饰.
主要方法:
- 来自活跃AS患者的外周血液单核细胞 (PBMC) 用Triptolide (TP) 或GSK-J4.4治疗.
- 流细胞计用于分析T淋巴细胞子集和IL-17表达.
- 为了评估关键的信号分子和表观遗传标记物 (RORγt,JMJD3,EZH2,JAK2,STAT3,H3K27me3),使用了ELISA,西斑和定量RT-PCR.
主要成果:
- 三胺 (TP) 和GSK-J4显著降低了AS患者的PBMC中的IL-17表达.
- TP治疗降低了RORγt,JAK2和STAT3.3的表达.
- TP上调了H3K27me3水平,在RORc,STAT3和IL-17基因促进器中进行了丰富,同时改变了JMJD3和EZH2的表达.
结论:
- 托利德通过调节表观遗传修饰,特别是H3K27me3,并影响基因素修饰酶JMJD3和EZH2.2,从而抑制AS中的Th17细胞分化.
- 这些发现为triptolide在AS的临床疗效提供了分子基础.
- 这项研究表明,结性脊柱炎的新疗法可能是潜在的分子标.
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