| First Author | Wang Y | Year | 2019 |
| Journal | Free Radic Biol Med | Volume | 131 |
| Pages | 237-242 | PubMed ID | 30503401 |
| Mgi Jnum | J:295493 | Mgi Id | MGI:6453879 |
| Doi | 10.1016/j.freeradbiomed.2018.11.037 | Citation | Wang Y, et al. (2019) Intraperitoneal injection of 4-hydroxynonenal (4-HNE), a lipid peroxidation product, exacerbates colonic inflammation through activation of Toll-like receptor 4 signaling. Free Radic Biol Med 131:237-242 |
| abstractText | 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. |
