Journal
MOLECULES
Volume 27, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/molecules27092990
Keywords
neuroinflammation; ST2825; BV2 microglia cells; lipopolysaccharide (LPS)
Funding
- CAMS Innovation Fund for Medical Sciences [2021-I2M-1-069]
- National Natural Science Foundation of China [81473383]
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The study found that ST2825 can inhibit neuroinflammation, reduce the levels of inflammatory factors, and exert its effects by inhibiting NF-kappa B activation and down-regulating the NLRP3/cleaved caspase-1 signaling pathway.
Neuroinflammation characterized by microglia activation is the mechanism of the occurrence and development of various central nervous system diseases. ST2825, as a peptide-mimetic MyD88 homodimerization inhibitor, has been identified as crucial molecule with an anti-inflammatory role in several immune cells, especially microglia. The purpose of the study was to investigate the anti-neuroinflammatory effects and the possible mechanism of ST2825. Methods: Lipopolysaccharide (LPS) was used to stimulate neuroinflammation in male BALB/c mice and BV2 microglia cells. The NO level was determined by Griess Reagents. The levels of pro-inflammatory cytokines and chemokines were determined by ELISA. The expressions of inflammatory proteins were determined by real-time PCR and Western blotting analysis. The level of ROS was detected by DCFH-DA staining. Results: In vivo, the improved levels of LPS-induced pro-inflammatory factors, including TNF-alpha, IL-6, IL-1 beta, MCP-1 and ICAM-1 in the cortex and hippocampus, were reduced after ST2825 treatment. In vitro, the levels of LPS-induced pro-inflammatory factors, including NO, TNF-alpha, IL-6, IL-1 beta, MCP-1, iNOS, COX2 and ROS, were remarkably decreased after ST2825 treatment. Further research found that the mechanism of its anti-neuroinflammatory effects appeared to be associated with inhibition of NF-kappa B activation and down-regulation of the NLRP3/cleaved caspase-1 signaling pathway. Conclusions: The current findings provide new insights into the activity and molecular mechanism of ST2825 for the treatment of neuroinflammation.
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