Division of Inflammation Research, Center for Molecular Medicine, General and Transplant Surgery, Jichi Medical University, Tochigi, Japan; Department of Surgery, Division of Gastroenterological, General and Transplant Surgery, Jichi Medical University, Tochigi, Japan.
Division of Inflammation Research, Center for Molecular Medicine, General and Transplant Surgery, Jichi Medical University, Tochigi, Japan.
Biochem Biophys Res Commun. 2019 Oct 29;519(1):15-22. doi: 10.1016/j.bbrc.2019.08.083. Epub 2019 Aug 28.
Intestinal ischemia/reperfusion (I/R) injury is a life-threatening complication that leads to inflammation and remote organ damage. However, the underlying mechanism is not yet fully understood. Toll-like receptor 5 (TLR5) is highly expressed in mucosa and recognizes flagellin, the main component of the bacterial flagella. Here, we investigated the role of TLR5 in inflammation and tissue damage after intestinal I/R injury using TLR5-deficient mice.
Intestinal levels of TLR5 mRNA and flagellin protein were elevated in wild-type mice subjected to intestinal I/R. Although TLR5 deficiency had no effect on intestinal flagellin levels, it significantly attenuated intestinal injury and inflammatory responses after intestinal I/R. TLR5 deficiency also markedly improved survival in mice after intestinal I/R injury. In wild-type mice, intestinal I/R injury induced remote organ damage, particularly in the lung, which was attenuated by TLR5 deficiency. Furthermore, TLR5 deficiency prevented lung inflammatory responses and vascular permeability after intestinal I/R injury.
These findings demonstrate a novel role of TLR5 and provide new insights into the mechanism underlying inflammation and tissue damage after intestinal I/R injury.
肠缺血/再灌注（I/R）损伤是一种危及生命的并发症，可导致炎症和远处器官损伤。然而，其潜在机制尚不完全清楚。Toll 样受体 5（TLR5）在黏膜中高度表达，可识别鞭毛蛋白，鞭毛蛋白是细菌鞭毛的主要成分。在这里，我们使用 TLR5 缺陷小鼠研究了 TLR5 在肠 I/R 损伤后炎症和组织损伤中的作用。
肠 I/R 后，野生型小鼠肠内 TLR5 mRNA 和鞭毛蛋白水平升高。尽管 TLR5 缺失对肠内鞭毛蛋白水平没有影响，但它显著减轻了肠 I/R 后的肠损伤和炎症反应。TLR5 缺失也显著提高了肠 I/R 损伤后小鼠的存活率。在野生型小鼠中，肠 I/R 损伤诱导了远处器官损伤，特别是在肺脏，而 TLR5 缺失可减轻这种损伤。此外，TLR5 缺失可预防肠 I/R 损伤后肺脏的炎症反应和血管通透性增加。
这些发现表明 TLR5 具有新的作用，并为肠 I/R 损伤后炎症和组织损伤的机制提供了新的见解。
