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Protective Role of the Toll-Like Receptor 5 Agonist KMRC011 against Murine Colitis Induced by Citrobacter rodentium and Dextran Sulfate Sodium

  • Jun-Young Kim (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University) ;
  • Sun-Min Seo (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University) ;
  • Han-Woong Kim (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University) ;
  • Woo-Jong Lee (CONNEXT Co. Ltd) ;
  • Yang-Kyu Choi (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University)
  • Received : 2022.09.29
  • Accepted : 2022.11.10
  • Published : 2023.01.28

Abstract

This study aimed to identify the therapeutic ability of a novel toll-like receptor (TLR) 5 agonist, KMRC011, on ulcerative colitis induced by Citrobacter rodentium and dextran sulfate sodium in a C57BL/6N mouse model. Ulcerative colitis was induced in the mice by the oral administration of 1% dextran sulfate sodium in sterile drinking water for seven days ad libitum, followed by C. rodentium infection on the seventh day by intra-gastric administration (DSS-CT group). KMRC011 was administered intramuscularly at both 24 h and 15 min before (Treatment 1 group), and at both 15 min and 24 h after (Treatment 2 group) the C. rodentium infection. The length of the large intestine and histopathological counts were significantly greater and mucosal thickness was significantly thinner in the Treatment 1 group compared to the DSS-CT and Treatment 2 groups. Il-6 and Il-10 mRNA expression levels were upregulated, while Ifn-γ and Tnf-α mRNA expression levels were significantly downregulated in the Treatment 1 group, compared to the DSS-CT group. NF-κB p65 expression level was elevated due to ulcerative colitis in the DSS-CT group, but was significantly downregulated in the Treatment 1 group. Overall, KMRC011 showed protective effects against murine colitis by inhibiting NF-κB signaling.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1A2C2005898) and the Civil-Military Technology Cooperation Program (14-CM-EB-09; NTIS 1695004819).

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