Abstract
Accidental radiation exposure causes the acute lethal damage of hematopoietic system and gastrointestinal tract1,2. By establishing an ionizing radiation (IR) induced injury model, we found macrophage-activating lipopeptide-2 (MALP-2) exhibited significant radioprotective effects in mice. MALP-2 improved the survival of irradiated mice, inhibited the radiation-induced gastrointestinal tract damage. Through intestinal organoid experiments, we found that MALP-2 protected the intestinal organoid against IR-induced injury. Next, we identified the differentially expressed genes (DEGs) between PBS and MALP-2 groups based on the RNA sequencing result3. And the RNA-seq results showed that MALP-2 increased the levels of interleukin 6 (IL-6), IL-12, G-CSF, GM-CSF, TNF-α, CCL-3, PGE-2 and SOD2. KEGG enrichment analysis showed that DEGs were significantly enriched in Toll-like receptor signaling pathway and NF-κB signaling pathway. In line with these observations, the expression level of IL-6 and GM-CSF were increased by using flow cytometry. Moreover, MALP-2 protected WT mice from IR induced death but had no radioprotective effects on the TLR2 KO and IL-6 KO mice, suggesting that the radioprotection of MALP-2 was mediated by activating TLR2/IL-6 axis. In conclusion, our data suggested that the MALP-2 could induce significant radioprotective effects and MALP-2 might be a potential radioprotective agent.