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Abstract
Exposure to ionizing radiation leads to severe damages in radiosensitive organs and induces acute radiation syndrome, including effects on the hematopoietic system and gastrointestinal system. In this study, the radioprotective ability of KMRC011, a novel toll-like receptor 5 (TLR5) agonist, was investigated in C57BL6/N mice exposed to lethal total-body gamma-irradiation. In a 30-day survival study, KMRC011-treated mice had a significantly improved survival rate compared with control after 11 Gy total-body irradiation (TBI), and it was found that the radioprotective activity of KMRC011 depended on its dosage and repeated treatment. In a 5-day short-term study, we demonstrated that KMRC011 treatment stimulated cell proliferation and had an anti-apoptotic effect. Furthermore, KMRC011 increased the expressions of genes related to DNA repair, such as Rad21, Gadd45b, Sod2 and Irg1, in the small intestine of lethally irradiated mice. Interestingly, downregulation of NF-κB p65 in the mouse intestine by KMRC011 treatment was observed. This data indicated that KMRC011 exerted a radioprotective activity partially by regulating NF-κB signaling. Finally, peak expression levels of G-CSF, IL-6, IFN-γ, TNF-α and IP-10 induced by KMRC011 treatment were different depending on the route of administration and type of cytokine. These cytokines could be used as candidate biomarkers for the evaluation of KMRC011 clinical efficacy. Our data indicated that KMRC011 has radioprotective activity in lethally irradiated mice and may be developed as a therapeutic agent for radioprotection.

Author information

Kim JY1, Park JH1,2, Seo SM1, Park JI1,2, Jeon HY1,3, Lee HK1, Yoo RJ4, Lee YJ4, Woo SK4, Lee WJ5, Choi CM5, Choi YK1.
1
Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea.
2
ViroMed Co., Ltd, 1, Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea.
3
Department of Core Research Laboratory, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, 892, Dongnam-ro, Gangdong-gu, Seoul, Republic of Korea.
4
Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 75, Nowon-ro, Nowon-gu, Seoul, Republic of Korea.
5
Biomedical Manufacturing Technology Center, Korea Institute of Industrial Technology, 59, Yangho-gil, Yeongcheon-si, Gyeongsangbuk-do, Republic of Korea.