快速诱导炎症性脂质介质的炎症体体体内体内的炎症体
Jakob von Moltke1, Norver J Trinidad, Mahtab Moayeri
1Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis, University of California at Berkeley, Berkeley, California 94720, USA.
Nature
|August 21, 2012
概括
主体炎症细胞通过"eicosanoid风暴",即大量释放信号脂质,在小鼠中引发快速死亡. 这种依赖于酶-1 (CASP1) 的先天免疫反应,绕过了IL-1β/IL-18的产生,突出了新的炎症酶功能.
科学领域:
- 免疫学 免疫学 免疫学
- 具有天生的免疫力.
- 分子生物学分子生物学
背景情况:
- 主体炎症细胞检测微生物产品,激活caspase-1 (CASP1) 来处理细胞因子并诱导热.
- NAIP5/NLRC4炎症体识别了细菌鞭毛蛋白,这是天生的免疫监测的关键组成部分.
研究的目的:
- 为了研究超出细胞因子处理的caspase-1 (CASP1) 的新型体内功能.
- 阐明了系统性炎症酶激活的快速宿主反应背后的机制.
主要方法:
- 细菌鞭素的系统输送,以激活小鼠的NAIP5/NLRC4炎症体.
- 评估生理反应,包括血管流体流失和死亡率.
- 分析炎症组分依赖性 (NAIP5,NLRC4,CASP1) 和细胞因子的产生 (IL-1β,IL-18).
- 使用缺乏循环氧化原酶-1的小鼠和细胞酸酸酶A2 (cPLA2) 激活研究,研究脂质介质参与.
主要成果:
- 系统性炎症酶激活由flagellin诱导的快速血管流体损失和死亡 (<30分钟) 在小鼠.
- 这种反应依赖NAIP5,NLRC4和CASP1,但独立于IL-1β或IL-18.
- 快速的"eicosanoid风暴" (前列腺素,白血) 被确定为炎症和血管泄漏的媒介.
- 缺乏循环氧化原酶-1 的小鼠对炎症酶诱导的病理学有抗性.
- 炎症酶激活触发了通过cPLA2在初始化腹巨细胞中的eicosanoid生物合成.
结论:
- 伊可索诺伊德代表了以前未被识别的,细胞类型特定的炎症体的信号输出.
- 这种途径在体内调解了快速,严重的生理后果,与正规的IL-1β/IL-18信号传输不同.
- 向eicosanoid生物合成可以提供治疗策略来对抗急性炎症性炎症性疾病.
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