Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, Shanghai, China.
J Cell Mol Med. 2021 Apr;25(8):3785-3792. doi: 10.1111/jcmm.16252. Epub 2021 Feb 19.
Severe ionizing radiation causes the acute lethal damage of haematopoietic system and gastrointestinal tract. Here, we found CL429, the novel chimeric TLR2/NOD2 agonist, exhibited significant radioprotective effects in mice. CL429 increased mice survival, protected mice against the lethal damage of haematopoietic system and gastrointestinal tract. CL429 was more effective than equivalent amounts of monospecific (TLR2 or NOD2) and combination (TLR2 + NOD2) of molecules in preventing radiation-induced death. The radioprotection of CL429 was mainly mediated by activating TLR2 and partially activating NOD2. CL429-induced radioprotection was largely dependent on the activation of TLR2-MyD88-NF-κB signalling pathway. In conclusion, the data suggested that the co-activation of TLR2 and NOD2 could induce significant synergistic radioprotective effects and CL429 might be a potential high-efficiency selective agent.
严重的电离辐射会导致造血系统和胃肠道的急性致命损伤。在这里，我们发现新型嵌合 TLR2/NOD2 激动剂 CL429 在小鼠中表现出显著的放射防护作用。CL429 提高了小鼠的存活率，保护了小鼠免受造血系统和胃肠道的致命损伤。CL429 在预防辐射诱导的死亡方面比同等剂量的单特异性（TLR2 或 NOD2）和组合（TLR2+NOD2）分子更有效。CL429 的放射防护主要通过激活 TLR2 和部分激活 NOD2 来介导。CL429 诱导的放射防护在很大程度上依赖于 TLR2-MyD88-NF-κB 信号通路的激活。总之，这些数据表明 TLR2 和 NOD2 的共同激活可以诱导显著的协同放射防护作用，CL429 可能是一种有潜力的高效选择性药物。
