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在体外,酸盐通过TGR5/β-arrestin2调节巨细胞的两极分化
Miao Liu1, Wen-Jie Xie2, Xu Zhang3
1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China.
Molecular medicine (Cambridge, Mass.)
|January 29, 2025
概括
甲酸 (SB) 向塔克达G蛋白结合受体5 (TGR5) 抑制M1巨细胞极化并促进M2极化,提供性结肠炎 (UC) 治疗的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 巨细胞是性结肠炎 (UC) 发病过程中的关键参与者.
- 研究巨细胞功能的调节剂对于UC治疗至关重要.
研究的目的:
- 探索甲酸盐 (SB) 对巨细胞功能的影响.
- 确定SB在调节巨细胞极化中的分子标和机制.
主要方法:
- 瑞士目标预测和表面等离子体共振 (SPR) 确定了Takeda的G蛋白结合受体5 (TGR5) 作为SB目标.
- 脂质蛋白解质量谱 (Lip-MS) 和分子对接揭示了TGR5.5上的SB结合点.
- 巨细胞极化在体外由脂聚糖 (LPS) 诱导,随后对带有和没有SB治疗的极化标志物进行了分析.
主要成果:
- SB逆转了巨细胞极化标记物LPS诱导的变化,包括IL-10,ARG1,CD206,IL-1β,iNOS和CD86.
- TGR5对抗性 (SBI-115) 和β-arrestin2倒退取消了SB的作用,而TGR5对抗性 (INT-777) 逆转了β-arrestin2倒退的抑制作用.
结论:
- 甲酸 (SB) 准TGR5并调节巨细胞极化.
- 在RAW264.7细胞中,SB抑制LPS诱导的M1型偏振,并通过TGR5/β-arrestin2通路促进M2型偏振.
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