德尔塔样4诱导巨细胞中痕信号传递:对炎症的影响
Erik Fung1, Sai-Man Timothy Tang, James P Canner
1Center for Excellence in Vascular Biology, Brigham and Women's Hospital, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA 02115, USA.
Circulation
|May 30, 2007
概括
德尔塔样4 (Dll4) 触发巨细胞中的Notch信号,促进炎症基因表达和激活. 这一途径涉及巨细胞驱动的炎症性疾病,如动脉样硬化.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 激活的巨细胞是炎症性疾病的关键参与者,包括动脉样硬化.
- 诺奇信号在巨细胞激活中的确切作用以前是不清楚的.
研究的目的:
- 研究Notch信号在巨细胞激活和炎症反应中的作用.
主要方法:
- 在人体巨细胞体外和动脉样硬化斑块中检查了Notch通路组件.
- 利用RNA干扰用于基因沉默和定量免疫组织化学.
- 评估了基因转录和通路激活 (MAPK,Akt,NF-κB).
主要成果:
- 巨细胞表达诺奇受体 (1-4),诺奇3在分化过程中增加.
- 促炎性刺激通过TLR4和NF-κB增加了类似德尔塔4 (Dll4) 的表达.
- Dll4诱导的Notch激活可以调节炎症基因 (iNOS,PTX3,Id1) 和炎症途径.
- 诺奇3敲击降低了促炎性基因转录.
- 在动脉样硬化斑块内的巨细胞中发现了Dll4和Notch成分.
结论:
- Dll4触发的Notch信号似乎调解了巨细胞的炎症反应.
- 这一途径可能有助于炎症性疾病的发病.
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