{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T21:24:35Z","timestamp":1778880275500,"version":"3.51.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,6,5]],"date-time":"2019-06-05T00:00:00Z","timestamp":1559692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Civil and Military Dual-use Technology Cooperation","award":["14-CM-EB-09"],"award-info":[{"award-number":["14-CM-EB-09"]}]},{"name":"Civil and Military Dual-use Technology Cooperation","award":["1695004819"],"award-info":[{"award-number":["1695004819"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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-\u03baB p65 in the mouse intestine by KMRC011 treatment was observed. This data indicated that KMRC011 exerted a radioprotective activity partially by regulating NF-\u03baB signaling. Finally, peak expression levels of G-CSF, IL-6, IFN-\u03b3, TNF-\u03b1 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.<\/jats:p>","DOI":"10.1093\/jrr\/rrz024","type":"journal-article","created":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T12:42:36Z","timestamp":1554986556000},"page":"432-441","source":"Crossref","is-referenced-by-count":18,"title":["Radioprotective effect of newly synthesized toll-like receptor 5 agonist, KMRC011, in mice exposed to total-body irradiation"],"prefix":"10.1093","volume":"60","author":[{"given":"Jun-Young","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jong-Hyung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea"},{"name":"ViroMed Co., Ltd, 1, Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun-Min","family":"Seo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Il","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea"},{"name":"ViroMed Co., Ltd, 1, Gwanak-ro, Gwanak-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee-Yeon","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea"},{"name":"Department of Core Research Laboratory, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, 892, Dongnam-ro, Gangdong-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Kyul","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran-Ji","family":"Yoo","sequence":"additional","affiliation":[{"name":"Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 75, Nowon-ro, Nowon-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 75, Nowon-ro, Nowon-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Keun","family":"Woo","sequence":"additional","affiliation":[{"name":"Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, 75, Nowon-ro, Nowon-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo-Jong","family":"Lee","sequence":"additional","affiliation":[{"name":"Biomedical Manufacturing Technology Center, Korea Institute of Industrial Technology, 59, Yangho-gil, Yeongcheon-si, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6292-6517","authenticated-orcid":false,"given":"Chi-Min","family":"Choi","sequence":"additional","affiliation":[{"name":"Biomedical Manufacturing Technology Center, Korea Institute of Industrial Technology, 59, Yangho-gil, Yeongcheon-si, Gyeongsangbuk-do, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4969-5443","authenticated-orcid":false,"given":"Yang-Kyu","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,6,5]]},"reference":[{"key":"2019071912395839800_rrz024C1","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1089\/ars.2013.5489","article-title":"Effects of ionizing radiation on biological molecules\u2014mechanisms of damage and emerging methods of detection","volume":"21","author":"Reisz","year":"2014","journal-title":"Antioxid Redox Signal"},{"key":"2019071912395839800_rrz024C2","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/med.21386","article-title":"Radioprotective agents: strategies and translational advances","volume":"36","author":"Kamran","year":"2016","journal-title":"Med Res Rev"},{"key":"2019071912395839800_rrz024C3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.4103\/2277-9175.115821","article-title":"A review on natural background radiation","volume":"2","author":"Sahbazi-Gahrouei","year":"2013","journal-title":"Adv Biomed Res"},{"key":"2019071912395839800_rrz024C4","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/s11684-012-0196-4","article-title":"Particle therapy for cancers: a new weapon in radiation therapy","volume":"6","author":"Jiang","year":"2012","journal-title":"Front Med"},{"key":"2019071912395839800_rrz024C5","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1126\/science.1166202","article-title":"p53 controls radiation-induced gastrointestinal syndrome in mice independent of apoptosis","volume":"327","author":"Kirsch","year":"2010","journal-title":"Science"},{"key":"2019071912395839800_rrz024C6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1080\/09553009414550101","article-title":"Characterization of radiation-induced apoptosis in the small-intestine and its biological implications","volume":"65","author":"Potten","year":"1994","journal-title":"Int J Radiat Biol"},{"key":"2019071912395839800_rrz024C7","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1667\/RR3104","article-title":"Radiation, the ideal cytotoxic agent for studying the cell biology of tissues such as the small intestine","volume":"161","author":"Potten","year":"2004","journal-title":"Radiat Res"},{"key":"2019071912395839800_rrz024C8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0300-483X(03)00149-5","article-title":"Protection against ionizing radiation by antioxidant nutrients and phytochemicals","volume":"189","author":"Weiss","year":"2003","journal-title":"Toxicology"},{"key":"2019071912395839800_rrz024C9","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1084\/jem.173.5.1177","article-title":"Role of cytokines (interleukin 1, tumor necrosis factor, and transforming growth factor beta) in natural and lipopolysaccharide-enhanced radioresistance","volume":"173","author":"Neta","year":"1991","journal-title":"J Exp Med"},{"key":"2019071912395839800_rrz024C10","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1126\/science.1154986","article-title":"An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models","volume":"320","author":"Burdelya","year":"2008","journal-title":"Science"},{"key":"2019071912395839800_rrz024C11","doi-asserted-by":"crossref","first-page":"e0135388","DOI":"10.1371\/journal.pone.0135388","article-title":"The toll-like receptor 5 agonist entolimod mitigates lethal acute radiation syndrome in non-human primates","volume":"10","author":"Krivokrysenko","year":"2015","journal-title":"PLoS One"},{"key":"2019071912395839800_rrz024C12","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.mrgentox.2014.09.001","article-title":"Activation of Toll-like receptors by intestinal microflora reduces radiation-induced DNA damage in mice","volume":"774","author":"Chen","year":"2014","journal-title":"Mutat Res Genet Toxicol Environ Mutagen"},{"key":"2019071912395839800_rrz024C13","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1667\/RR0758.1","article-title":"Manganese superoxide dismutase (SOD2)-mediated delayed radioprotection induced by the free thiol form of amifostine and tumor necrosis factor alpha","volume":"167","author":"Murley","year":"2007","journal-title":"Radiat Res"},{"key":"2019071912395839800_rrz024C14","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.bbrc.2018.11.080","article-title":"TLR5 binding and activation by KMRC011, a flagellin-derived radiation countermeasure","volume":"508","author":"Song","year":"2019","journal-title":"Biochem Biophys Res Commun"},{"key":"2019071912395839800_rrz024C15","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3322\/caac.21349","article-title":"Cancer treatment and survivorship statistics, 2016","volume":"66","author":"Miller","year":"2016","journal-title":"CA Cancer J Clin"},{"key":"2019071912395839800_rrz024C16","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/nrc1950","article-title":"Preventing or reducing late side effects of radiation therapy: radiobiology meets molecular pathology","volume":"6","author":"Bentzen","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"2019071912395839800_rrz024C17","doi-asserted-by":"crossref","first-page":"8280","DOI":"10.4049\/jimmunol.180.12.8280","article-title":"Flagellin treatment protects against chemicals, bacteria, viruses, and radiation","volume":"180","author":"Vijay-Kumar","year":"2008","journal-title":"J Immunol"},{"key":"2019071912395839800_rrz024C18","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1667\/RR14514.1","article-title":"Mitigation of radiation-induced epithelial damage by the TLR5 agonist entolimod in a mouse model of fractionated head and neck irradiation","volume":"187","author":"Toshkov","year":"2017","journal-title":"Radiat Res"},{"key":"2019071912395839800_rrz024C19","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2131\/fts.5.33","article-title":"Subacute toxicity evaluation of KMRC011, a Toll-like receptor-5 agonist administered by intramuscular injection to rats","volume":"5","author":"Kang","year":"2018","journal-title":"Fundam Toxicol Sci"},{"key":"2019071912395839800_rrz024C20","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/jat.3719","article-title":"Repeated injection of KMRC011, a medical countermeasure for radiation, can cause adverse health effects in cynomolgus monkeys","volume":"39","author":"Lee","year":"2019","journal-title":"J Appl Toxicol"},{"key":"2019071912395839800_rrz024C21","doi-asserted-by":"crossref","first-page":"e66586","DOI":"10.1371\/journal.pone.0066586","article-title":"CpG-oligodeoxynucleotide treatment protects against ionizing radiation-induced intestine injury","volume":"8","author":"Zhang","year":"2013","journal-title":"PLoS One"},{"key":"2019071912395839800_rrz024C22","doi-asserted-by":"crossref","first-page":"4763","DOI":"10.7314\/APJCP.2012.13.9.4763","article-title":"Toll-like receptor 5 agonism protects mice from radiation pneumonitis and pulmonary fibrosis","volume":"13","author":"Wang","year":"2012","journal-title":"Asian Pac J Cancer Prev"},{"key":"2019071912395839800_rrz024C23","doi-asserted-by":"crossref","first-page":"6605","DOI":"10.1093\/nar\/20.24.6605","article-title":"Cloning and characterization of rad21 an essential gene of Schizosaccharomyces pombe involved in DNA double-strand-break repair","volume":"20","author":"Birkenbihl","year":"1992","journal-title":"Nucleic Acids Res"},{"key":"2019071912395839800_rrz024C24","doi-asserted-by":"crossref","first-page":"7703","DOI":"10.1074\/jbc.270.13.7703","article-title":"The rad21 gene-product of Schizosaccharomyces pombe is a nuclear, cell cycle\u2013regulated phosphoprotein","volume":"270","author":"Birkenbihl","year":"1995","journal-title":"J Biol Chem"},{"key":"2019071912395839800_rrz024C25","doi-asserted-by":"crossref","first-page":"17552","DOI":"10.1074\/jbc.M600950200","article-title":"Gadd45a and Gadd45b protect hematopoietic cells from UV-induced apoptosis via distinct signaling pathways, including p38 activation and JNK inhibition","volume":"281","author":"Gupta","year":"2006","journal-title":"J Biol Chem"},{"key":"2019071912395839800_rrz024C26","doi-asserted-by":"crossref","first-page":"e42224","DOI":"10.1371\/journal.pone.0042224","article-title":"Exposure to heavy ion radiation induces persistent oxidative stress in mouse intestine","volume":"7","author":"Datta","year":"2012","journal-title":"PLoS One"},{"key":"2019071912395839800_rrz024C27","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/j.bcp.2006.08.023","article-title":"20 years of NF-kappaB","volume":"72","author":"Chariot","year":"2006","journal-title":"Biochem Pharmacol"},{"key":"2019071912395839800_rrz024C28","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1126\/science.1215584","article-title":"Structural basis of TLR5-flagellin recognition and signaling","volume":"335","author":"Yoon","year":"2012","journal-title":"Science"},{"key":"2019071912395839800_rrz024C29","doi-asserted-by":"crossref","first-page":"e0174474","DOI":"10.1371\/journal.pone.0174474","article-title":"Melatonin protects rats from radiotherapy-induced small intestine toxicity","volume":"12","author":"Fernandez","year":"2017","journal-title":"PLoS One"},{"key":"2019071912395839800_rrz024C30","doi-asserted-by":"crossref","first-page":"301","DOI":"10.21037\/atm.2016.08.25","article-title":"CBLB502 administration protects gut mucosal tissue in ulcerative colitis by inhibiting inflammation","volume":"4","author":"Xu","year":"2016","journal-title":"Ann Transl Med"},{"key":"2019071912395839800_rrz024C31","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/biolre\/ioy173","article-title":"CBLB502, a Toll-like receptor 5 agonist, offers protection against radiation-induced male reproductive system damage in mice","volume":"100","author":"Bai","year":"2019","journal-title":"Biol Reprod"},{"key":"2019071912395839800_rrz024C32","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1172\/JCI115354","article-title":"Ionizing radiation induces expression and binding activity of the nuclear factor kappa B","volume":"88","author":"Brach","year":"1991","journal-title":"J Clin Invest"},{"key":"2019071912395839800_rrz024C33","doi-asserted-by":"crossref","first-page":"23061","DOI":"10.1074\/jbc.274.33.23061","article-title":"Heat shock inhibits radiation-induced activation of NF-kappa B via inhibition of I-kappa B kinase","volume":"274","author":"Curry","year":"1999","journal-title":"J Biol Chem"},{"key":"2019071912395839800_rrz024C34","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1124\/jpet.112.196071","article-title":"Identification of granulocyte colony-stimulating factor and interleukin-6 as candidate biomarkers of CBLB502 efficacy as a medical radiation countermeasure","volume":"343","author":"Krivokrysenko","year":"2012","journal-title":"J Pharmacol Exp Ther"},{"key":"2019071912395839800_rrz024C35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.cyto.2014.08.003","article-title":"Colony-stimulating factors for the treatment of the hematopoietic component of the acute radiation syndrome (H-ARS): a review","volume":"71","author":"Singh","year":"2015","journal-title":"Cytokine"}],"container-title":["Journal of Radiation Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jrr\/advance-article-pdf\/doi\/10.1093\/jrr\/rrz024\/28767690\/rrz024.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jrr\/article-pdf\/60\/4\/432\/28964344\/rrz024.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T12:40:19Z","timestamp":1563540019000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jrr\/article\/60\/4\/432\/5511450"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,5]]},"references-count":35,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,6,5]]},"published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jrr\/rrz024","relation":{},"ISSN":["0449-3060","1349-9157"],"issn-type":[{"value":"0449-3060","type":"print"},{"value":"1349-9157","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,7]]},"published":{"date-parts":[[2019,6,5]]}}}