在败血症中,BAP31通过NF-κB信号通路促进内皮细胞和巨细胞之间的粘附
Jiawei He1, Danyang Jing1, Shen Zhao1
1Department of Critical Care Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Journal of inflammation research
|March 4, 2024
概括
B细胞受体关联蛋白31 (BAP31) 通过增加内皮细胞粘附分子来促进败血症. 在败血症模型中减少BAP31通过抑制炎症信号通路来降低死亡率和器官损伤.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 病理生理学 病理生理学
背景情况:
- 败血症是一种危及生命的器官功能障碍,是由宿主对感染的反应失调引起的.
- 内皮细胞的激活在败血症的发病过程中起着至关重要的作用,导致炎症和器官损伤.
- 在败血症中潜在的内皮细胞功能障碍的特定分子机制需要进一步阐明.
研究的目的:
- 研究B细胞受体关联蛋白31 (BAP31) 在败血症的发病过程中的作用.
- 确定BAP31对败血症期间内皮细胞激活和炎症反应的影响.
- 阐明在败血症中受到BAP31影响的信号通路.
主要方法:
- 已确立的结和刺穿 (CLP) 诱导的小鼠模型和LPS挑战的人类脉内皮细胞 (HUVEC) 模型用于败血症.
- 在体内和体外分别使用了Cre/LoxP和shRNA来进行BAP31的敲击.
- 采用中性粒细胞/巨细胞-内皮细胞共同培养,西式涂抹,qRT-PCR,IHC和IF来分析细胞透,粘附,基因/蛋白质表达和信号通路 (TLR,TAK1,PI3K/AKT).
主要成果:
- 在小鼠中,BAP31 knockdown显著降低了CLP诱导的死亡率,组织学损伤和中性粒细胞/巨细胞透.
- BAP31的淘汰降低了内皮细胞中的ICAM1和VCAM1表达,削弱了中性粒细胞和巨细胞的粘附.
- BAP31 knockdown减弱了TLR4,TAK1,PI3K/AKT和NF-κB信号通路的LPS诱导激活,并减少了亲炎性细胞因子的产生.
结论:
- BAP31在内皮细胞中的ICAM1和VCAM1上调,有助于与败血症相关的器官损伤.
- BAP31在败血症发病过程中的作用涉及TLR,TAK1和PI3K-AKT信号通路的调节.
- 向BAP31可能是缓解败血症引起的炎症和器官损伤的治疗策略.
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