Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist

Zhiqiang Hu, Yaling Xing, Yuanyu Qian, Xiaojuan Chen, Jian Tu, Lening Ren, Kai Wang, Zhongbin Chen*

*Corresponding author for this work

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    A number of agents are now available for use in protecting against ionizing radiation. These radiation-protective agents, however, have many adverse effects. Efforts have been made to develop new radiation-protective agents for medical application. Here, we investigated whether a compound, polyethylenimine (PEI), which activates Toll-like receptor 5 (TLR5)-mediated NF-kB signaling pathways, could have an anti-radiation effect on a mouse model. First, a cell-based screening model for an agonist of TLR5-mediated NF-kB pathway was established and then validated by activation of TLR5-mediated NF-kB luciferase reporter activity with a known TLR5 agonist, flagellin. We found that PEI induced dose-dependent activation of the TLR5-mediated NF-kB pathway, indicating that PEI is indeed a TLR5 agonist. Furthermore, the anti-radiation effect of polyethylenimine was assessed using a γ-ray total body irradiation (TBI) mouse model. Compared with the irradiation control, both survival time and survival rate were significantly improved in mice that received either a low dose of polyethylenimine (P= 0.019) or a high dose of polyethylenimine (P< 0.001). We also observed a positive correlation between animal body weight and survival time in mice that received a low dose of polyethylenimine, a high dose of polyethylenimine and amifostine, over a period of 30 days, r= 0.42 (P< 0.02), 0.72 (P< 0.0001) and 0.95 (P< 0.0001), respectively, while a negative correlation between animal body weight and survival time was observed in the irradiation control (r= -0.89; P< 0.0001). These results indicate that polyethylenimine is a new TLR5 agonist with potential application in offering protection for patients receiving radiotherapy or in radiation-related accidents.

    Original languageEnglish
    Pages (from-to)243-250
    Number of pages8
    JournalJournal of Radiation Research
    Volume54
    Issue number2
    DOIs
    Publication statusPublished - Mar 2013

    Keywords

    • NF-κB
    • Polyethylenimine (PEI)
    • radiation protection
    • Toll-like receptor 5 (TLR5)
    • total body irradiation (TBI)

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