Key Laboratory of Precision Nutrition and Food Quality, Department of Nutrition and Health, China Agricultural University, Beijing, 100193, China.
College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
Food Chem Toxicol. 2024 Oct;192:114966. doi: 10.1016/j.fct.2024.114966. Epub 2024 Aug 26.
Advanced glycation end products (AGEs) are a spectrum of complex compounds widely found in processed foods and frequently consumed by humans. AGEs are implicated in impairing the intestinal barrier, but the underlying mechanisms remain unclear. This study investigated the effects of three types of AGEs on gene expression of tight junctions (TJs) in colorectal epithelial HT-29 cells, and observed minimal alterations in TJs expression. Given the important role of subepithelial macrophages in regulating the intestinal barrier, we explored whether AGEs affect the intestinal barrier via the involvement of macrophages. Notably, a significant downregulation of TJs expression was observed when supernatants from AGEs-treated RAW264.7 macrophage cells were transferred to HT-29 cells. Further investigations indicated that AGEs increased IL-6 levels in RAW264.7 cells, subsequently triggering STAT3 activation and suppressing TJs expression in HT-29 cells. The role of STAT3 activation was confirmed by observing enhanced TJs expression in HT-29 cells following pretreatment with an inhibitor of STAT3 activation prior to the transfer of the conditioned medium. These findings demonstrated that AGEs impaired the intestinal barrier via macrophage-mediated STAT3 activation, shedding light on the mechanisms underlying AGEs-induced intestinal barrier injury and related food safety risks.
晚期糖基化终产物 (AGEs) 是一类广泛存在于加工食品中并经常被人类摄入的复杂化合物。AGEs 被认为会损害肠道屏障，但潜在机制尚不清楚。本研究探讨了三种类型的 AGEs 对结直肠上皮 HT-29 细胞中紧密连接 (TJ) 基因表达的影响，观察到 TJ 表达的微小变化。鉴于黏膜下巨噬细胞在调节肠道屏障中的重要作用，我们探讨了 AGEs 是否通过巨噬细胞的参与影响肠道屏障。值得注意的是，当将 AGEs 处理的 RAW264.7 巨噬细胞细胞上清液转移至 HT-29 细胞时，观察到 TJ 表达明显下调。进一步的研究表明，AGEs 增加了 RAW264.7 细胞中的 IL-6 水平，随后触发 STAT3 激活并抑制 HT-29 细胞中的 TJ 表达。通过观察到在转移条件培养基之前用 STAT3 激活抑制剂预处理 HT-29 细胞后 TJ 表达增强，证实了 STAT3 激活的作用。这些发现表明，AGEs 通过巨噬细胞介导的 STAT3 激活损害肠道屏障，揭示了 AGEs 诱导的肠道屏障损伤和相关食品安全风险的潜在机制。
