Novel chimeric TLR2/NOD2 agonist CL429 exhibited significant radioprotective effects in mice.
Acetylmuramyl-Alanyl-Isoglutamine
/ analogs & derivatives
Acute Radiation Syndrome
/ etiology
Animals
Hematopoietic System
/ drug effects
Intestines
/ drug effects
Male
Mice
Mice, Inbred C57BL
Nod2 Signaling Adaptor Protein
/ agonists
Radiation-Protective Agents
/ pharmacology
Toll-Like Receptor 2
/ agonists
Whole-Body Irradiation
/ adverse effects
Cl429
NOD2
TLR2
radiation
radioprotection
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
revised:
27
11
2020
received:
15
09
2020
accepted:
17
12
2020
pubmed:
21
2
2021
medline:
23
9
2021
entrez:
20
2
2021
Statut:
ppublish
Résumé
Severe ionizing radiation causes the acute lethal damage of haematopoietic system and gastrointestinal tract. Here, we found CL429, the novel chimeric TLR2/NOD2 agonist, exhibited significant radioprotective effects in mice. CL429 increased mice survival, protected mice against the lethal damage of haematopoietic system and gastrointestinal tract. CL429 was more effective than equivalent amounts of monospecific (TLR2 or NOD2) and combination (TLR2 + NOD2) of molecules in preventing radiation-induced death. The radioprotection of CL429 was mainly mediated by activating TLR2 and partially activating NOD2. CL429-induced radioprotection was largely dependent on the activation of TLR2-MyD88-NF-κB signalling pathway. In conclusion, the data suggested that the co-activation of TLR2 and NOD2 could induce significant synergistic radioprotective effects and CL429 might be a potential high-efficiency selective agent.
Identifiants
pubmed: 33609010
doi: 10.1111/jcmm.16252
pmc: PMC8051721
doi:
Substances chimiques
Nod2 Signaling Adaptor Protein
0
Nod2 protein, mouse
0
Radiation-Protective Agents
0
TLR2-NOD2 agonist CL429
0
Tlr2 protein, mouse
0
Toll-Like Receptor 2
0
Acetylmuramyl-Alanyl-Isoglutamine
53678-77-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3785-3792Subventions
Organisme : National Natural Science Foundation of China
ID : 81872559
Organisme : National Natural Science Foundation of China
ID : 81903260
Organisme : National Natural Science Foundation of China
ID : 31800705
Organisme : Shanghai Sailing Program
ID : 19YF1459100
Informations de copyright
© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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