巨细胞杯作为mTORC2-AKT通路的信号平台,以调节巨细胞中LPS诱导的细胞因子表达
Li Wang1, Xiaowei Sun1, Jianan Chen2,3
1State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.
Journal of leukocyte biology
|March 21, 2024
概括
巨细胞体杯对于脂聚糖 (LPS) 诱导的AKT通路激活和巨细胞中细胞因子释放至关重要. 抑制巨细胞酶或AKT会减少促炎性细胞因子的表达,这表明巨细胞酶是治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 巨型皮诺细胞症是一种摄入大颗粒的细胞过程,主要在细胞中.
- 来自格拉姆阴性细菌的脂多糖 (LPS) 在巨细胞中触发巨细胞酶.
- 巨型皮诺细胞体会影响细胞信号通路,包括AKT通路.
研究的目的:
- 调查巨细胞杯在LPS诱导的AKT酸化 (pAKT) 和细胞因子表达中的作用.
- 阐明连接巨型皮诺细胞体,AKT激活和细胞因子生产的信号机制.
- 探索巨细胞作为调节炎症反应的潜在治疗点.
主要方法:
- 高分辨率扫描电子显微镜可可视化巨型皮诺细胞杯结构.
- 同焦显微镜以确定杯子内AKT和mTORC2的定位.
- 生物化学测试,RNA测序,qPCR和ELISA用于分析信号通路和细胞因子表达.
- 针对巨细胞和AKT通路的抑制研究.
主要成果:
- 经过LPS刺激,可以在巨细胞中诱导特定的巨细胞杯结构.
- AKT和mTORC2被定位在这些巨细胞杯中.
- 抑制巨细胞酶阻断了LPS诱导的pAKT和随后的炎症性细胞因子 (IL-6,IL-1α) 表达.
- 抑制巨细胞结核或AKT受损的核因子 κB (NF-κB) 激活.
- 巨细胞杯作为AKT通路激活的信号平台.
结论:
- 由LPS诱导的巨细胞杯是巨细胞中AKT通路激活的重要信号平台.
- AKT/IκB/NF-κB通路由巨细胞结核调节,可以控制促炎性细胞因子的表达.
- 巨型皮诺细胞症是控制炎症性细胞因子生产的有前途的治疗标.
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