加斯德明D调节了巨细胞中可溶性fms类铁酶-1的释放
Hazuki Tanaka1, Ren Ozawa1, Yuka Henmi1
1Laboratory of Animal Reproduction, Department of Animal Science, Tokyo University of Agriculture, Japan.
Reproductive biology
|January 31, 2024
概括
人类巨细胞通过气体皮质蛋白D (GSDMD) 通过可溶性fms类型的氨酸激酶 (sFLT1) 分泌,这是一种涉及孕前 (PE) 病理学的途径. 这种sFLT1释放与cathepsin B有关,而不是NLRP3炎症酶激活.
科学领域:
- 免疫学 免疫学 免疫学
- 病理学 病理学 病理学
- 细胞生物学 细胞生物学
背景情况:
- 孕前 (PE) 是一种严重的妊娠并发症,与胎盘可溶性fms类氨酸激酶 (sFLT1) 有关.
- 虽然热囊细胞是主要来源,但胎盘单细胞/巨细胞也分泌sFLT1.1.
- NLRP3炎症酶和气皮素D (GSDMD) 调节的热与PE的发病有关.
研究的目的:
- 调查人类单细胞/巨细胞THP-1细胞是否分泌依赖NLRP3炎症体和GSDMD的sFLT1.
- 探索GSDMD和cathepsin B在sFLT1分泌中的作用.
主要方法:
- 使用博12-米里酸13-酸盐 (PMA) 将THP-1单细胞分化为巨细胞.
- 使用了NLRP3,caspase-1和GSDMD的基因删除和药理抑制剂.
- 评估sFLT1和IL-1β分泌和细胞死亡.
- 通过使用CA074-ME.ME研究了cathepsin B的作用.
主要成果:
- 在THP-1巨细胞中,PMA诱导了sFLT1和IL-1β的分泌,但没有导致细胞死亡.
- NLRP3炎症酶组件 (NLRP3,卡斯帕酶-1) 对sFLT1分泌没有必要.
- 删除或抑制GSDMD显著降低了IL-1β和sFLT1分泌.
- 素B的抑制也降低了sFLT1和IL-1β的释放.
结论:
- THP-1巨细胞以GSDMD依赖的方式释放sFLT1,但不是NLRP3炎症酶依赖的方式.
- 这种由GSDMD介导的sFLT1释放可能涉及GSDMD的非性功能.
- sFLT1分泌与PMA刺激的巨细胞中的lysosomal cathepsin B活性有关,这表明PE病理学中的作用.
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