释放的dDNA触发性炎症酶作为肠道辐射保护点
Long Chen1,2, Ziwen Wang3, Jie Wu1
1State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine Army Medical University Chongqing China.
Clinical & translational immunology
|June 19, 2023
概括
放射治疗通过自身dsDNA引发巨细胞中的炎症体引起肠道粘膜炎. 迪苏尔菲拉姆 (DSF) 抑制了这种途径,为辐射引起的肠损伤提供了潜在的治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 胃肠病学 胃肠病学
- 在瘤学瘤学.
背景情况:
- 肠道粘膜炎是放射治疗的重要副作用之一.
- 驱动肠道粘膜炎的特定免疫原体尚未完全理解.
- 目前仅有有限的辐射保护剂可供使用.
研究的目的:
- 为了研究双链DNA (dsDNA) 触发的炎症体在辐射诱导的肠粘膜炎中的作用.
- 为了确定潜在的免疫原体,负责肠道放射性毒性.
- 探索缓解肠道粘膜炎的治疗策略.
主要方法:
- 针对促炎性细胞因子的ELISA.
- 辐射诱导肠道损伤的小鼠模型 (生存率,体重,组织学,屏障功能).
- 西部斑点,免疫光,共免疫沉和流动细胞测量以分析dSDNA和炎症酶激活.
主要成果:
- 升高的IL-1β和IL-18与放射治疗患者的腹相关.
- 被辐射的肠上皮细胞 (IECs) 释放dDNA,作为免疫原体.
- dsDNA通过HMGB1/RAGE激活巨细胞中的AIM2炎症酶,增加IL-1β和IL-18.
- 迪苏尔菲拉姆 (DSF) 通过抑制炎症酶来减轻肠道放射性毒性.
结论:
- 辐射IECs的细胞外自我dsDNA是一种免疫原,可触发肠道粘膜炎.
- 向巨细胞中dDNA触发的炎症酶是一种有前途的治疗策略,用于放射治疗的副作用.
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