死亡细胞释放的染色蛋白HMGB1会引发炎症
Paola Scaffidi1, Tom Misteli, Marco E Bianchi
1DIBIT, Istituto Scientifico San Raffaele, 20132 Milano, Italy.
Nature
|July 12, 2002
概括
高流动性组1 (HMGB1) 蛋白质信号细胞死亡和炎症. 死亡细胞释放HMGB1,而亡细胞保留它,防止炎症反应.
科学领域:
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 高流动性1组 (HMGB1) 蛋白质既可以作为细胞内架构的染色质结合因子,也可以作为细胞外炎症媒介.
- 细胞外HMGB1与高级糖化终产品 (RAGE) 的受体结合,引发炎症反应.
- HMGB1是由激活的免疫细胞释放的,并且被受损或死细胞被动释放.
研究的目的:
- 调查HMGB1释放在信号细胞死亡和启动炎症中的作用.
- 根据HMGB1释放来区分死细胞与亡细胞的炎症潜力.
- 阐明控制HMGB1在亡期间释放的机制.
主要方法:
- 在缺乏HMGB1 (Hmgb1(-/-) 的死细胞中分析炎症.
- 在死细胞和死细胞细胞之间的HMGB1释放和炎症潜力的比较.
- 在改变基因组乙化条件下,研究HMGB1染色质结合和释放在细胞中.
主要成果:
- 死细胞的Hmgb1 ((-/-) 细胞显著降低了炎症能力,证实了HMGB1作为损伤信号的作用.
- 亡细胞,即使是经历二次亡的细胞,也未能释放HMGB1并没有促进炎症.
- 在亡细胞中,HMGB1由于基因素低乙化而与染色质保持紧密结合;防止脱乙化阻止了HMGB1的释放.
结论:
- HMGB1释放是细胞死亡引起的炎症的关键信号,特别是来自死细胞或创伤性损伤的细胞.
- 亡细胞被编程为隔离HMGB1,从而积极阻止炎症信号的广播.
- 基素乙化状态决定了HMGB1的释放和随后的死亡细胞中的炎症信号.
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