通过组织微环境控制炎症反应.
Zhongyang Wu1,2, Scott D Pope3,4, Nasiha S Ahmed5
1Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
巨细胞在炎症期间感觉到酸性环境. 这种由BRD4调节的pH传感调节基因表达和炎症反应,提供关键的反来控制炎症.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 炎症是一种关键的防御机制,但可以损害正常的生理功能.
- 监测炎症的负面后果的机制尚不清楚.
- 组织微环境的酸化是已知的炎症的标志.
研究的目的:
- 调查巨细胞是否能感知组织酸化以调节炎症反应.
- 确定将pH值变化与炎症基因调节联系起来的分子机制.
主要方法:
- 巨细胞培养和体内模型被用于研究炎症反应.
- 用基因表达分析和生物化学测试来评估pH依赖的效应.
- 在pH感应中研究了含有马素的蛋白4 (BRD4) 在pH感应中的作用.
主要成果:
- 酸性pH以一种特定的方式重组了巨细胞炎症基因表达.
- 哺乳动物含原蛋白4 (BRD4) 被确定为一种新的细胞内pH传感器.
- 酸性pH破坏了含BRD4和MED1的转录凝聚物,通过胺丰富的区域.
- 降低巨细胞内pH值调节体外和体内转录凝聚物,提供负面反.
结论:
- 在转录凝聚物中发现了一个依赖pH值的开关,该开关将环境传感与直接控制炎症联系起来.
- 证明了巨细胞细胞内pH值的降低对于调节炎症反应至关重要.
- 这些发现表明,根据炎症成本,对校准炎症大小和质量有更广泛的意义.
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