相关实验视频
通过RANKL/RANKL对发烧和女性体温进行中央控制
Reiko Hanada1, Andreas Leibbrandt, Toshikatsu Hanada
1IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, 1030 Vienna, Austria.
Nature
|November 27, 2009
概括
NF-kappaB连接体 (RANKL) 的受体激活剂及其受体RANK对于大脑温度调节至关重要. 这些分子控制发烧反应,并影响女性的正常体温,揭示了骨重塑之外的新角色.
科学领域:
- 神经免疫学 神经免疫学
- 神经内分泌学神经内分泌学
- 生理学 生理学 生理学
背景情况:
- NF-kappaB连接体 (RANKL) 的受体激活剂及其受体RANK是已知的骨重塑,淋巴结发育和乳腺功能的调节者.
- RANKL和RANK在中枢神经系统中表达,但它们在大脑中的功能在很大程度上是未知的.
- 在温度调节和发烧反应中RANKL/RANK信号的作用尚未被探索.
研究的目的:
- 为了研究RANKL/RANK信号在大脑中的功能相关性.
- 确定RANKL/RANK在发烧反应和温度调节中的作用.
- 阐明RANKL/RANK介导发烧所涉及的特定细胞类型和分子通路.
主要方法:
- 在小鼠和老鼠中注射RANKL,以评估发烧反应.
- 生产和利用组织特异的Nestin-Cre和GFAP-Cre排名 (化) 删除剂小鼠,将RANK功能映射到星球细胞.
- 评估转基因小鼠对脂聚糖 (LPS),IL-1β和TNFalpha的发烧反应.
- 热调节通路的分析,包括COX2-PGE(2) /EP3R信号传递.
- 在肺炎期间对患有RANK突变的儿童及其发烧反应的临床观察.
主要成果:
- 中央RANKL注射在小鼠和老鼠中引起严重发烧.
- 星球细胞中的RANK信号被确定为对发烧反应至关重要.
- 纳斯-克雷和GFAP-克雷等级的小鼠对LPS-,IL-1β-和TNFalpha诱导的发烧有抗性.
- 通过COX2-PGE(2) /EP3R通路,RANKL/RANK信号激活了温度调节的大脑区域.
- 雌性小鼠在星细胞中缺乏RANK,表现出改变的基底体温.
- 患有RANK突变的儿童在肺炎期间表现出发烧反应受损.
结论:
- 在发烧的中央调节中,RANKL/RANK信号发挥着至关重要的,以前未被认可的作用.
- 星球细胞是RANKL/RANK诱导的发烧反应的关键媒介.
- 这种信号通路涉及炎症发烧和正常的女性温度调节,突出了这些骨质细胞分化因子的新功能.
相关概念视频
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01:19Homeostatic Imbalances in Body Temperature
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