人类上皮细胞对TNF的反应涉及一种可诱导的自身分泌级联
Kevin A Janes1, Suzanne Gaudet, John G Albeck
1Center for Cell Decision Processes, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Cell
|March 28, 2006
概括
瘤亡因子 (TNF) 触发细胞死亡和生存信号. 这项研究揭示了TNF启动了信号的"自身分泌级联",通过复杂的交叉通话影响细胞命运.
科学领域:
- 细胞生物学 细胞生物学
- 分子信号传递是分子信号传递.
背景情况:
- 瘤亡因子 (TNF) 是一种促炎性细胞因子,在亡中具有双重作用.
- 了解TNF受体 (TNFR) 信号通路之间的交叉交谈对于确定细胞命运至关重要.
- 敌对的亲和反apoptotic信号之间的交叉语音的机制仍然在很大程度上是未知的.
研究的目的:
- 为了研究在人类上皮细胞中生长TNF和生存增长因子信号传递之间的交叉声.
- 阐明TNF启动的间接信号通路.
主要方法:
- 实验和计算分析.
- 基于分类器的回归的应用.
- 一个细胞因子信号汇编的分析,其中包括8000个细胞内蛋白质测量.
主要成果:
- TNF通过激活的TNFR引起直接反应和间接反应.
- 间接反应涉及转化生长因子-α (TGF-alpha),互白素-1alpha (IL-1alpha) 和IL-1受体对手 (IL-1ra) 的连续释放.
- 这一由TNF诱导的随机,时间变化的细胞外信号序列被称为"自林级联".
结论:
- 由TNF诱导的自身分泌级联涉及协同和对抗信号电路之间的复杂交叉声.
- 这种交叉语音将细胞反应与当地的微环境联系起来.
- 对这些自身分泌级联的进一步研究可以提供关于细胞对炎症信号的反应的见解.
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