Oncotarget

Research Papers:

Monophosphoryl lipid a attenuates radiation injury through TLR4 activation

Jiaming Guo, Yuanyuan Chen, Xiao Lei, Yang Xu, Zhe Liu, Jianming Cai, Fu Gao and Yanyong Yang _

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Oncotarget. 2017; 8:86031-86042. https://doi.org/10.18632/oncotarget.20907

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Abstract

Jiaming Guo1,*, Yuanyuan Chen1,*, Xiao Lei1,*, Yang Xu1, Zhe Liu1, Jianming Cai1, Fu Gao1 and Yanyong Yang1

1Department of Radiation Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai, 200433, 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

Jianming Cai, email: cjm882003@163.com

Keywords: monophosphoryl lipid a (MPLA), radioprotection, toll like receptor 4 (TLR4), TRIF, MyD88

Received: June 16, 2017    Accepted: August 04, 2017    Published: September 15, 2017

ABSTRACT

Ionizing radiation causes severe damage to human body, and normal tissue toxicity in cancer radiotherapy also limits its further application. It is urgently required to develop safe and effective radioprotector. Our previous study has shown that toll like receptor 4 (TLR4) was dispensable for basal radiation resistance. However, severe toxicity of its traditional agonist lipopolysaccharide limits the clinical application. In present study, we demonstrated that monophosphoryl lipid A (MPLA), a potent TLR4 agonist with low toxicity, effectively attenuated radiation injury on in vitro and in vivo. MPLA increased cell survival and inhibited cell apoptosis after irradiation, and cell cycle arrest was also inhibited. Radiosensitive tissues including spleen, intestine, bone marrow and testis were protected from radiation damages in a TLR4 dependent manner. We also found that myeloid differentiation factor 88 (MyD88) accounted more than Toll/IL-1R domain-containing adaptor inducing IFN-β (TRIF) for the radioprotective effects of MPLA. In conclusion, our finding suggests TLR4 agonist MPLA as a safe and effective radioprotector for clinical application.


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