DNA-PKcs是通过免疫刺激DNA激活先天免疫的必要条件
1The Sam and Rose Stein Institute for Research on Aging, University of California, San Diego 9500 Gilman Drive 92093, La Jolla, CA, USA. wmchu@ucsd.edu
Cell
|January 4, 2001
概括
细菌DNA和合成免疫刺激性寡氧氧核糖核酸 (ISS-ODN) 激活了天生的免疫力. DNA-PKcs和IKKbeta对于这种细胞因子反应至关重要,将DNA修复与免疫信号联系起来.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 具有天生的免疫力.
- DNA 检测 检测 检测 检测
背景情况:
- 众所周知,细菌DNA和合成免疫刺激性寡氧氧核糖核酸 (ISS-ODN) 能够刺激先天免疫反应.
- 细菌DNA和ISS-ODN发出信号的确切分子机制尚未确定.
- 了解这些途径对于开发新型免疫疗法和了解宿主防御至关重要.
研究的目的:
- 阐明细菌DNA和ISS-ODN在先天免疫中的分子识别机制.
- 研究DNA-PKcs和IKKbeta在这些分子激活的信号通路中的作用.
- 建立DNA修复途径和先天免疫反应之间的联系.
主要方法:
- 将细菌DNA和ISS-ODN给缺乏DNA-PK (DNA-PKcs) 催化子单元的小鼠.
- 在实验室中刺激来自野生类型和淘汰赛小鼠 (DNA-PKcs/和IKKbeta-/-) 的骨髓衍生巨细胞 (BMDM).
- 测量细胞因子诱导 (IL-6和IL-12) 和评估NF-kappaB激活.
主要成果:
- 缺乏DNA-PKcs的小鼠在服用细菌DNA和ISS-ODN时表现出IL-6和IL-12的缺陷诱导.
- 发现DNA-PKcs和IKKbeta都对正常的细胞因子产生至关重要,以应对细菌DNA和ISS-ODN.
- 细菌DNA和ISS-ODN激活DNA-PK,这随后有助于激活IKK和NF-kappaB.
结论:
- DNA-PKcs在对细菌DNA和ISS-ODN的先天性免疫反应中起着新的和必不可少的作用.
- 在DNA修复机制 (DNA-PKcs) 和先天免疫信号通路之间建立了直接联系.
- 这些发现揭示了DNA-PKcs和IKKbeta是细菌DNA和ISS-ODN启动的信号级联中的关键组成部分.
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