Heat-killed salmonella typhimurium (HKST) protects mice against radiation in TLR4-dependent manner
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Yang Xu1,*, Yuanyuan Chen1,*, Hu Liu1,*, Xiao Lei1, Jiaming Guo1, Kun Cao1, Cong Liu1, Bailong Li1, Jianming Cai1, Jintao Ju2, Fu Gao1 and Yanyong Yang1
1Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, P.R. China
2Faculty of Naval Medicine, Second Military Medical University, 200433, Shanghai, P.R. China
*These authors have contributed equally to this work
Yanyong Yang, email: [email protected]
Fu Gao, email: [email protected]
Jintao Ju, email: [email protected]
Keywords: HKST, radioprotection, TLR, radiosensitive tissues, DNA damage
Received: February 09, 2017 Accepted: April 04, 2017 Published: May 15, 2017
It is urgently required to develop novel safe and effective radioprotectors to alleviate radiation damages. Recently, several toll like receptors (TLRs), including TLR2, TLR4, TLR5, TLR9, have been proved to exert protective effects against ionizing radiation. Due to different tissue-distribution and distinct functions of TLRs, we hypothesized that co-activation of multiple TLRs simultaneously may produce extensive and stronger radioprotective effects. In this study, we found the co-agonist of TLR2, TLR4 and TLR5, heat-killed salmonella typhimurium (HKST) significantly inhibited radiation-induced cell apoptosis, increased cell survival and alleviated DNA damage. HKST also prolonged animal survival and protected radiosensitive tissues against radiation damages, such as bone marrow, spleen and testis. Decrease of CD4+ and CD8+ cells were also reversed by HKST treatment. By using TLR2 and TLR4 knockout mice, we found that most of radioprotective effects of HKST were abrogated in TLR4 knock out mice. And HKST failed to inhibited cell apoptosis in TLR5 knock down cells. In conclusion, we demonstrated that HKST effectively protected cells and radiosensitive tissues against radiation injury in a TLR4 biased mechanism, suggesting HKST as a potential radioprotector with low toxicity.
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