Oncotarget

Research Papers:

Heat-killed salmonella typhimurium (HKST) protects mice against radiation in TLR4-dependent manner

Yang Xu, Yuanyuan Chen, Hu Liu, Xiao Lei, Jiaming Guo, Kun Cao, Cong Liu, Bailong Li, Jianming Cai, Jintao Ju, Fu Gao and Yanyong Yang _

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Oncotarget. 2017; 8:67082-67093. https://doi.org/10.18632/oncotarget.17859

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Abstract

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

Correspondence to:

Yanyong Yang, email: yyyang2010@163.com

Fu Gao, email: gaofusmmu@163.com

Jintao Ju, email: jujt0827@sina.com

Keywords: HKST, radioprotection, TLR, radiosensitive tissues, DNA damage

Received: February 09, 2017    Accepted: April 04, 2017    Published: May 15, 2017

ABSTRACT

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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