title: Anti-radiation damage effect of polyethylenimine as a toll-like receptor 5 targeted agonist.
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.
authors.affiliation: Division of Infection and Immunity, Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Hu
authors.forename: Yaling
authors.initials: Y
authors.lastname: Xing
authors.forename: Yuanyu
authors.initials: Y
authors.lastname: Qian
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Tu
authors.forename: Lening
authors.initials: L
authors.lastname: Ren
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Chen
mesh_terms: D054508:Acute Radiation Syndrome / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D011094:Polyethyleneimine / Q000008:administration & dosage*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D015996:Survival Rate; D051198:Toll-Like Receptor 5 / Q000819:agonists* / Q000378:metabolism*; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D016328:NF-kappa B; D011837:Radiation-Protective Agents; D051198:Toll-Like Receptor 5; D011094:Polyethyleneimine