Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Inflammation. 2011 Oct;34(5):440-7. doi: 10.1007/s10753-010-9251-y.
Oxidative stress and inflammatory cytokines such as TNF-α are thought to be involved in mucosal inflammation. The intestinal epithelium may be concurrently stimulated by both oxidative stress and inflammatory cytokines during the inflammation process in the intestines. However, experimental models for intestinal inflammation still employ single stimulation, either by an oxidative stress or inflammatory cytokine. We therefore examined an in vitro inflammation study using human intestinal epithelial Caco-2 cells, in which the cells were stimulated both by hydrogen peroxide and TNF-α, and measured the IL-8 production as an index of inflammation. The IL-8 production (secretion, mRNA expression, and transcriptional activity) induced by both TNF-α and H(2)O(2) was significantly higher than that by single stimulation. The synergistic effect of TNF-α and H(2)O(2) on the NF-κB signaling pathway (transcriptional activity and p65 nuclear translocation) was also observed. Oxidative stress and TNF-α may cooperatively enhance IL-8 production via NF-κB in Caco-2 cells.
氧化应激和 TNF-α 等炎症细胞因子被认为参与了黏膜炎症。在肠道炎症过程中，肠道上皮细胞可能同时受到氧化应激和炎症细胞因子的刺激。然而，肠道炎症的实验模型仍然采用单一刺激，要么是氧化应激，要么是炎症细胞因子。因此，我们使用人肠上皮细胞 Caco-2 细胞进行了体外炎症研究，其中细胞同时受到过氧化氢和 TNF-α的刺激，并测量了作为炎症指标的 IL-8 产生。TNF-α和 H₂O₂诱导的 IL-8 产生（分泌、mRNA 表达和转录活性）明显高于单一刺激。还观察到 TNF-α和 H₂O₂对 NF-κB 信号通路（转录活性和 p65 核转位）的协同作用。氧化应激和 TNF-α可能通过 Caco-2 细胞中的 NF-κB 协同增强 IL-8 的产生。
