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先进的糖化终产物 (AGEs) 通过巨细胞介导的STAT3激活来损害肠上皮屏障

Xin Qiang¹, Shumin Liang¹, Yinchuan Lv¹

¹Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, 100193, China.

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association

|August 28, 2024

概括

加工食品中的高级糖化终产品 (AGEs) 损害了肠道屏障. AGEs激活巨细胞,然后向肠道细胞发出信号,通过IL-6和STAT3通路损害屏障功能.

科学领域:

食品科学与营养食品科学与营养
胃肠病学胃肠病学
免疫学免疫学免疫学

背景情况:

先进的糖化终产品 (AGEs) 在加工食品中普遍存在.
AGEs与肠道屏障功能障碍有关,但机制尚不清楚.
巨细胞在维护肠道屏障完整性方面发挥着关键作用.

研究的目的:

研究AGE对肠上皮质紧接点 (TJs) 的影响.
探索巨细胞在AGE诱导的肠道屏障损伤中的作用.
阐明涉及IL-6和STAT3.3的分子机制.

主要方法:

暴露HT-29结直肠上皮细胞三种类型的AGE.
用AGEs对RAW264.7巨细胞进行处理,并将条件介质转移到HT-29细胞.
对TJ基因表达,IL-6水平和STAT3激活的分析.
使用STAT3激活抑制剂来确认途径的参与.

主要成果:

直接AGE暴露对HT-29细胞中的TJ表达影响最小.
来自AGE处理的巨细胞的超活体显著降低了HT-29细胞中的TJ表达.
AGEs在巨细胞中增加IL-6,在HT-29细胞中激活STAT3,并抑制TJs.
STAT3抑制逆转了AGE引起的TJ下调.

结论:

AGEs主要通过巨细胞介导的途径损害肠道屏障.
该机制涉及巨细胞的AGE诱导的IL-6产生,导致肠道细胞中的STAT3激活.
这项研究揭示了AGE诱导的肠损伤的新型机制,与食品安全相关.

关键词:

先进的糖化最终产品 (AGEs)肠道上皮质屏障肠道上皮质屏障巨细胞是一个巨细胞.在STAT3激活过程中,

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