在人类诱导的多能干细胞干细胞衍生的心肌细胞中,鞭毛素诱导的免疫反应
Goekhan Yuecel1,2, Xiaobo Zhou1,2, Linda Terkatz1,3
1Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
病原体相关的分子模式 (PAMPs) 通过通类受体 (TLR) 信号触发了败血性心肌病. 这项研究表明,人类诱导的多能干细胞衍生的心肌细胞 (hiPSC-CMs) 可以模拟心脏细胞中PAMP诱导的免疫反应.
科学领域:
- 免疫学 免疫学 免疫学
- 心脏病学 心脏病学
- 干细胞生物学 干细胞生物学
背景情况:
- 败血症引起的心肌病包括病原体相关的分子模式 (PAMPs) 和收费类受体 (TLR) 免疫反应.
- 人类诱导的多能干细胞衍生心肌细胞 (hiPSC-CMs) 为研究心肌细胞天生的免疫提供了一个模型.
研究的目的:
- 为了调查PAMP诱导的hiPSC-CMs的变化.
- 评估hiPSC-CMs作为研究PAMP介导心肌细胞反应的体外模型的实用性.
主要方法:
- 来自两名健康捐赠者的hiPSC-CM暴露于一种PAMP的鞭毛素 (FLA).
- 使用PCR,ELISA和FACS评估细胞因子表达 (TNFα),炎症途径 (caspase-8),TLR5信号,活性氧物种和表面抗原.
主要成果:
- 更高的FLA剂量增加了TNFα和caspase-8的表达.
- 长时间的FLA暴露增加了TLR5的表达和细胞表面比例.
- 在hiPSC-CMs中,FLA诱导可检测的先天免疫反应.
结论:
- hiPSC-CMs有效地模拟心肌细胞中PAMP诱导的先天免疫反应.
- 这种体外模型可用于研究败血性心肌病的机制.
- 通过TLR介导的信号传递是PAMP诱导的心肌细胞炎症的关键途径.
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