Intraperitoneal injection of 4-hydroxynonenal (4-HNE), a lipid peroxidation product, exacerbates colonic inflammation through activation of Toll-like receptor 4 signaling
Intraperitoneal injection of 4-hydroxynonenal (4-HNE), a lipid peroxidation product, exacerbates colonic inflammation through activation of Toll-like receptor 4 signaling
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腹腔注射 4-羟基壬烯醛 (4-HNE)（一种脂质过氧化产物）可通过激活 Toll 样受体 4 信号传导加剧结肠炎症
DOI：
10.1016/j.freeradbiomed.2018.11.037
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发表时间：
2019-02-01
影响因子：
7.4
通讯作者：
Zhang, Guodong
中科院分区：
文献类型：
--
作者：
Wang, Yuxin;Wang, Weicang;Zhang, Guodong
人类和动物研究表明，在炎症性肠病（IBD）中，脂质过氧化产物（如4-羟基壬烯醛（4-HNE））的结肠浓度升高。然而，这些化合物在IBD发展中的作用和机制尚不清楚。本研究表明，低剂量4-HNE全身治疗会加重C57BL/6小鼠右旋糖酐硫酸钠（DSS）诱导的IBD，表明其在体内具有促IBD作用。4- hne抑制了紧密连接蛋白occludin的结肠表达，损害了肠道屏障功能，增强了脂多糖（LPS）和细菌产物从肠道进入体循环的易位，导致体内toll样受体4 （TLR4）信号的激活增加。此外，在Tlr4（-/-）小鼠中，4-HNE未能促进dss诱导的IBD，这支持Tlr4信号参与了4-HNE的促IBD作用。综上所述，这些结果表明，4-HNE通过激活TLR4信号通路加速IBD的进展，因此可能参与IBD的发病机制。
Human and animal studies have shown that the colonic concentrations of lipid peroxidation products, such as 4-hydroxynonenal (4-HNE), are elevated in inflammatory bowel disease (IBD). However, the actions and mechanisms of these compounds on the development of IBD are unknown. Here, we show that a systemic treatment of low-dose 4-HNE exacerbates dextran sulfate sodium (DSS)-induced IBD in C57BL/6 mice, suggesting its pro-IBD actions in vivo. Treatment with 4-HNE suppressed colonic expressions of tight-junction protein occludin, impaired intestinal barrier function, enhanced translocation of lipopolysaccharide (LPS) and bacterial products from the gut into systemic circulation, leading to increased activation of Toll-like receptor 4 (TLR4) signaling in vivo. Furthermore, 4-HNE failed to promote DSS-induced IBD in Tlr4(-/-) mice, supporting that TLR4 signaling contributes to the pro-IBD effects of 4-HNE. Together, these results suggest that 4-HNE exacerbates the progression of IBD through activation of TLR4 signaling, and therefore could contribute to the pathogenesis of IBD.