Dectin-1在curdlan诱导的慢性肉芽肿病高炎症反应中的作用机制

发布时间：2018-04-24 00:19

本文选题：慢性肉芽肿性疾病 + curdlan　；参考：《生物化学与生物物理进展》2016年06期

【摘要】：慢性肉芽肿病(CGD)是一种罕见的遗传免疫缺陷综合症.CGD病人最常见为NADPH氧化酶2(NADPH oxidase 2,NOX2)功能缺失造成吞噬细胞内活性氧生成障碍,不能清除外源的细菌与真菌的感染.凝胶多糖curdlan属于1,3-β-葡聚糖,是白色念珠菌细胞壁的主要成分.目前,作为吞噬细胞中主要的模式识别受体,凝集素dectin-1是否参与curdlan诱导巨噬细胞参与免疫炎症反应以及其分子机制不十分清楚.为了研究这一机制,我们采用luminol和Amplex Red法检测活性氧生成水平,ELISA检测炎症因子IL-1β水平以及免疫荧光法检测NF-κB信号通路的激活情况.结果表明,curdlan浓度依赖性上调巨噬细胞活性氧生成,NOX2缺失显著降低活性氧产生,dectin-1缺失部分降低活性氧的生成和部分阻断NF-κB信号通路的激活.NOX2 KO小鼠炎症因子IL-1β水平显著升高,Dectin-1缺失后NOX2 KO小鼠IL-1β水平降低;Dectin-1 KO小鼠的IL-1β水平与WT小鼠比无显著差异,与Dectin-1/NOX2 KO小鼠比差异显著.上述结果提示,curdlan刺激下机体通过巨噬细胞内的dectin-1受体诱导免疫应答,激活NF-KB信号通路释放炎症因子IL-1β,同时通过dectin-1受体激活NOX2释放活性氧清除病原,促进机体修复.在这一过程中dectin-1不是唯一参与的受体.
[Abstract]:Chronic granulomatosis (CGD) is a rare genetic immunodeficiency syndrome. CGD is the most common cause of NADPH oxidase 2(NADPH oxidase 2 NOX2) deficiency resulting in dysfunction of reactive oxygen species production in phagocytes and the inability to remove exogenous bacterial and fungal infections. Gel polysaccharide (curdlan) is a major component of the cell wall of Candida albicans. At present, as the main pattern recognition receptor in phagocytes, it is not clear whether lectin dectin-1 is involved in curdlan induced macrophage immune inflammation and its molecular mechanism. In order to study this mechanism, luminol and Amplex Red were used to detect the level of reactive oxygen species (Ros) production and the level of inflammatory factor IL-1 尾 was detected by Elisa and the activation of NF- 魏 B signaling pathway was detected by immunofluorescence assay. The results showed that curdlan up-regulated the deletion of reactive oxygen species in macrophages in a dose-dependent manner. The deletion of dectin-1 decreased the production of reactive oxygen species and partially blocked the activation of NF- 魏 B signaling pathway. The level of inflammatory factor IL-1 尾 was partly blocked in mice with NF- 魏 B signaling pathway. There was no significant difference in the level of IL-1 尾 between NOX2 KO mice and WT mice after dectin-1 deletion. The difference was significant compared with Dectin-1/NOX2 KO mice. These results suggest that curdlan stimulates immune response through dectin-1 receptors in macrophages, activates the NF-KB signaling pathway to release inflammatory factor IL-1 尾, and activates the release of active oxygen species (Ros) through dectin-1 receptors to clear the pathogen and promote the body's repair. Dectin-1 is not the only receptor involved in this process.
【作者单位】：北京医院卫生部北京老年医学研究所卫生部老年医学重点实验室;
【基金】：国家自然科学基金(81400790,81061120527,81370445,81472408) 卫生部公益性研究基金(201302008) 国家科技部十二五支撑计划(2012BAI10B01)资助项目~~
【分类号】：R593.9

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