通过合成基因素模仿剂抑制炎症
Edwige Nicodeme1, Kate L Jeffrey, Uwe Schaefer
1Centre de Recherche GSK, 27 Avenue du Québec, 91140 Villebon Sur Yvette, France.
Nature
|November 12, 2010
概括
一种新的合成化合物,I-BET,通过破坏免疫细胞中的基因子识别来向炎症基因表达. 这种方法为开发免疫调节药物来对抗炎症疾病提供了一种新的策略.
科学领域:
- 免疫学 免疫学 免疫学
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 病原体与免疫细胞的相互作用会触发炎症基因表达,这对于防御至关重要,但由于过度的蛋白质生产,通常是有害的.
- 炎症反应的大小取决于上游信号蛋白和调节mRNA表达的染色体复合体.
- 核蛋白对转化后修改的基因组的识别对于启动mRNA转录和延长至关重要.
研究的目的:
- 提出一种针对炎症基因表达的新型药理学策略.
- 为了研究原蛋白和额外终端域 (BET) 蛋白质对乙化组合素识别的干扰.
- 评估一种合成化合物 (I-BET) 作为一种免疫调节药物的潜力.
主要方法:
- 开发一种合成化合物,I-BET,旨在模仿乙化组织蛋白.
- 测试I-BET在激活的巨细胞中破坏参与炎症基因表达的染色体复合物的能力.
- 在体内评估I-BET对脂聚糖诱导的内毒性休克和细菌诱导的败血症的保护作用.
主要成果:
- 合成化合物I-BET有效地模仿乙化组织蛋白,干扰BET蛋白识别.
- I-BET 破坏染色体复合体,显著降低激活巨细胞中关键炎症基因的表达.
- 在实验模型中,I-BET的使用使得对内毒性休克和细菌性败血症均有保护作用.
结论:
- 准识别翻译后修饰的组织蛋白的蛋白质代表了一个新的治疗途径.
- 像I-BET这样的合成化合物可以通过干扰表观遗传读者来调节炎症基因表达.
- 这种方法有望开发新一代免疫调节药物治疗炎症疾病.
相关概念视频
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