JCC:IL-6缺失会加剧IL-10缺乏小鼠的结肠炎并诱发全身性炎症

2019-11-09 不详 MedSci原创

白介素6(IL-6)或其受体目前是炎症性肠病(IBD)靶向生物治疗的候选药物。因此,必须全面了解阻断IL-6的后果。本项研究旨在通过评估IL-6缺失对IL-10缺陷小鼠(IL-10 -/-)自发性结肠炎的影响来预测相关后果。

背景和目标
白介素6(IL-6)或其受体目前是炎症性肠病(IBD)靶向生物治疗的候选药物。因此,必须全面了解阻断IL-6的后果。本项研究旨在通过评估IL-6缺失对IL-10缺陷小鼠(IL-10 -/-)自发性结肠炎的影响来预测相关后果。

方法
研究人员构建了IL-6 / IL-10双缺陷小鼠(IL-6 -/- / IL-10 -/-),并与WT和IL-10 -/-小鼠相比分析结肠粘膜的肠道炎症,一般表型和分子/生化的变化。

结果
出乎意料的是,在肠道炎症和全身炎症的比较中,IL-6 -/- / IL-10 -/-小鼠表现出比IL-10 -/ -小鼠更明显的肠道炎症和更早的疾病发作,白细胞增多,中性粒细胞增多和单核细胞增多。IL-6 -/- / IL-10 -/-小鼠表现出多种细胞因子(IL-1β,IL-4,IL-12,TNFα)和趋化因子(MCP-1和MIG)的升高。FOXP3和TGF-β,对于调节性T(Treg细胞)细胞分化的两个关键因素,在结肠黏膜中均显着下调。当IL-6 -/- / IL-10 -/-小鼠的结肠粘膜中iNOS上调时,CTLA-4减少。

结论
在IL-10 -/-小鼠中,完全的IL-6阻断至少部分通过抑制Treg / CTLA-4并促进IL-1β/ Th2途径显着加重了肠道炎症。

原始出处:

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    2019-11-10 kzlchina
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    2019-11-10 jjjiang0202
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    2019-11-09 txqjm

    谢谢了,学习

    0

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