塞拉斯特通过降低HDAC3 / FOXO3 / GLS1依赖的谷氨酸分解来减弱Th17细胞的反应
Yan Liu1, Wenjie Zhang1, Yilei Guo1
1Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 639 Long Mian Avenue, Nanjing 211198, China.
概括
塞拉斯特通过通过HDAC3/FOXO3/GLS途径降低谷氨酸分解的调节来抑制Th17细胞分化. 这一发现突出了塞拉斯特的存在.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞的新陈代谢
- 药理学 药理学是指药理学的学科.
背景情况:
- (Tripterygium wilfordii) 提取物在中国传统医学中用于治疗自身免疫性疾病.
- 赛拉斯特是一种关键成分,已知会影响Th17细胞分化,这在自身免疫中至关重要.
- 塞拉斯特对Th17细胞的确切作用机制需要阐明.
研究的目的:
- 为了研究塞拉斯特对Th17细胞反应的影响.
- 为了探索底层机制,专注于细胞代谢.
主要方法:
- 来自小鼠的原发性CD4+T细胞在Th17分化条件下进行培养.
- 使用流式细胞计,RT-qPCR和西部斑点来评估Th17细胞标记物和蛋白质水平.
- 使用生物化学测定和分子技术分析了谷氨胺代谢,HDAC活性和基因调节.
- 研究人员使用了硫酸 (DSS) 诱导的大肠炎的小鼠模型.
主要成果:
- 塞拉斯特以剂量依赖的方式抑制了Th17细胞的分化.
- 塞拉斯特通过降低谷氨酶1 (GLS1) 表达的调节来抑制谷氨溶解.
- 塞拉斯特增强了基因素脱乙酶3 (HDAC3) 的活性,导致FOXO3的乙化和表达增加,这反过来抑制了GLS1.1.
- 切拉斯特对Th17细胞的治疗效果在DSS诱导的大肠炎模型中得到证实.
结论:
- 塞拉斯特通过抑制依赖HDAC3/FOXO3/GLS的谷氨酸溶解途径来缓解Th17细胞反应.
- 塞拉斯特显示出作为一种治疗性药物,可以治疗由Th17细胞激活驱动的自身免疫性疾病.
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