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

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

Our previous works revealed the regulation of antiviral innate immune response through TLR signal transduction [15, 21] . We have also observed TLR5 receptor activated by a linear PEI in vitro in a separate study. This study found that branched PEI can activate the hTLR5-mediated NF-κB signaling pathway in a dose-dependent manner in a cell model. This finding is in agreement with a previous study using linear PEI that activated murine TLR5-mediated NF-κB signaling pathway [13] . The current study provides evidence that branched PEI offers radiation protection in addition to a previous report that a combination of linear PEI and siRNA produces immunostimulation in ovarian carcinoma mice [13] . The mechanism and effect of PEI are very similar to flagellin protein. It is interesting to note that the PEI used in our experiments is a chemical compound with a molecular weight of~25 kDa, and the molecular weight of flagellin protein ranges from 30 kDa to 60 kDa. Therefore, PEI may offer the following advantages over flagellin protein: (1) higher pharmacological specificity than flagellin protein [22, 23] ; (2) requires a lower dose than flagellin protein to achieve the same effect [11] ; (3) easier to Fig. 3 . Anti-radiation damage effect of polyethylenimine in an in vivo mice model. Forty-one mice were randomly divided into four groups, and injected with saline (n = 10), AMI (150 mg/kg, n = 10), PEI (5 mg/kg, n = 10) and PEI (10 mg/kg, n = 11), respectively. Animals were injected with different agents 30 min before an 8-Gy 60 Co γ-ray total body irradiation (TBI). (A) PEI significantly increased the survival rate of the radiated mice in a dose-dependent manner. Compared with IR mock, animal survival time and survival rate were significantly improved in mice that received a low dose of PEI (P = 0.019), or high dose of PEI (P < 0.001). (B) Body weight of surviving irradiated animals that received a low dose of PEI, high dose of PEI or AMI, was increased with time over a period of 30 days (r = 0.42, P < 0.02; 0.72, P < 0.0001; 0.95, P < 0.0001, respectively). Animal body weight in IR mock declined with time (r = -0.89; P < 0.0001). be delivered to its targets [24, 25] ; and (4) stable in storage at room temperature [26, 27] .