1. Academic Validation
  2. Intravenous immunoglobulin protects the integrity of the intestinal epithelial barrier and inhibits ferroptosis induced by radiation exposure by activating the mTOR pathway

Intravenous immunoglobulin protects the integrity of the intestinal epithelial barrier and inhibits ferroptosis induced by radiation exposure by activating the mTOR pathway

  • Int Immunopharmacol. 2024 Mar 21:131:111908. doi: 10.1016/j.intimp.2024.111908.
Jia He 1 Peng Jiang 1 Li Ma 1 Fengjuan Liu 1 Ping Fu 1 Xi Du 1 Zhenni Xu 2 Jun Xu 3 Lu Cheng 3 Zongkui Wang 4 Changqing Li 5 Dengqun Liu 6
Affiliations

Affiliations

  • 1 Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu, Sichuan Province 610052, China.
  • 2 Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan Province 610041, China.
  • 3 Shanghai RAAS Blood Products Co., Ltd., Shanghai 201401, China.
  • 4 Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu, Sichuan Province 610052, China. Electronic address: zongkui.wang@ibt.pumc.edu.cn.
  • 5 Institute of Blood Transfusion, Chinese Academy of Medical Sciences & Peking Union Medical College, Chengdu, Sichuan Province 610052, China. Electronic address: lcq@ibt.pumc.edu.cn.
  • 6 Radiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan Province 610041, China. Electronic address: dengqunliu@uestc.edu.cn.
Abstract

Radiation exposure often leads to serious health problems in humans. The intestinal epithelium is sensitive to radiation damage, and radiation causes destruction of the intestinal epithelial barrier, which leads to radiation enteritis (RE), the loss of fluids, and the translocation of intestinal bacteria and toxins; radiation can even threaten survival. In this study, we aimed to explore the influence of IVIg on the integrity of the intestinal epithelial barrier after RE. Using a RE mouse model, we investigated the protective effects of intravenous immunoglobulin (IVIg) on the epithelial junctions of RE mice and validated these findings with intestinal organoids cultured in vitro. In addition, transmission electron microscopy (TEM), western blotting (WB) and immunostaining were used to further investigate changes in intestinal epithelial Ferroptosis and related signaling pathways. When RE occurs, the intestinal epithelial barrier is severely damaged. IVIg treatment significantly ameliorated this damage to epithelial tight junctions both in vivo and in vitro. Notably, IVIg alleviated RE by inhibiting intestinal epithelial Ferroptosis in RE mice. Mechanistically, IVIg promoted activation of the mTOR pathway and inhibited Ferroptosis in the intestinal epithelium of mice. Rapamycin, which is a potent inhibitor of the mTOR protein, significantly abolished the protective effect of IVIg against radiation-induced damage to intestinal epithelial tight junctions. Overall, IVIg can prevent RE-induced damage to the intestinal epithelial barrier and inhibit Ferroptosis by activating the mTOR pathway; this study provides a new treatment strategy for patients with RE caused by radiotherapy or accidental nuclear exposure.

Keywords

Epithelial barrier; Ferroptosis; Intravenous immunoglobulin; Radiation enteritis; mTOR pathway.

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