高频重复磁刺激通过调节p62/Keap1/Nrf2和p38 MAPK通路激活了巨细胞的杀菌活性
Therese B Deramaudt1, Ahmad Chehaitly1, Théo Charrière1
1U1179 INSERM, END-ICAP, UFR des Sciences de la Santé-Simone Veil, Université de Versailles Saint-Quentin-en-Yvelines, 78180 Montigny-le-Bretonneux, France.
Antioxidants (Basel, Switzerland)
|September 28, 2023
概括
重复磁刺激 (rMS) 激活了巨细胞中的Nrf2通路,增强了它们对抗金黄色葡萄球菌感染的能力. 这种免疫调节为细菌防御提供了一种新的治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 重复磁性刺激 (rMS) 的效应主要研究在易刺激的细胞中.
- 有限的研究存在于rMS对巨细胞等不可激发细胞的影响.
- 巨细胞是先天免疫防御的关键参与者.
研究的目的:
- 研究rMS对巨细胞功能的影响.
- 确定rMS是否可以增强巨细胞对细菌病原体的防御.
- 探索巨细胞中rMS的潜在分子机制.
主要方法:
- 从THP-1衍生出来的巨细胞在5分钟内受到10Hz的rMS.
- 分析了Nrf2激活,Keap1表达和p62酸化.
- 评估了黄金葡萄球菌 (Staphylococcus aureus) 的细胞内生存率.
- 使用Nrf2沉默 (siRNA) 和淘汰性巨细胞来确认Nrf2依赖性.
- 测量了炎症性基因表达 (IL-1β,TNF-α) 和p38 MAPK激活.
主要成果:
- rMS增加了Nrf2激活,并降低了巨细胞中的Keap1表达.
- Nrf2通路的激活取决于rMS诱导的p62酸化.
- rMS显著降低了细胞内黄金葡萄球菌的存活率.
- Nrf2沉默或淘汰消除了rMS的抗菌作用.
- rMS减弱了S. aureus诱导的IL-1β和TNF-α的表达,并抑制了p38 MAPK的激活.
结论:
- rMS激活了巨细胞中非正规的Nrf2通路.
- rMS调节巨细胞功能,增强宿主对细菌感染的防御能力.
- rMS显示出作为一种治疗策略来对抗细菌病原体的潜力.
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