A single injection of ng level of malp2 are sufficient to save 50 percent of lethally irradiated mice

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.