ST2825, a Small Molecule Inhibitor of MyD88, Suppresses NF-κB Activation and the ROS/NLRP3/Cleaved Caspase-1 Signaling Pathway to Attenuate Lipopolysaccharide-Stimulated Neuroinflammation
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-α, IL-6, IL-1β, 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-α, IL-6, IL-1β, 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-κB 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Molecules (Basel, Switzerland) - 27(2022), 9 vom: 06. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Shan-Shan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 19.05.2022 Date Revised 16.07.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/molecules27092990 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM340892838 |
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| 100 | 1 | |a Zhang, Shan-Shan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ST2825, a Small Molecule Inhibitor of MyD88, Suppresses NF-κB Activation and the ROS/NLRP3/Cleaved Caspase-1 Signaling Pathway to Attenuate Lipopolysaccharide-Stimulated Neuroinflammation |
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| 500 | |a Date Completed 19.05.2022 | ||
| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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-α, IL-6, IL-1β, 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-α, IL-6, IL-1β, 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-κB 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BV2 microglia cells | |
| 650 | 4 | |a ST2825 | |
| 650 | 4 | |a lipopolysaccharide (LPS) | |
| 650 | 4 | |a neuroinflammation | |
| 650 | 7 | |a Heterocyclic Compounds, 2-Ring |2 NLM | |
| 650 | 7 | |a Interleukin-6 |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a Myd88 protein, mouse |2 NLM | |
| 650 | 7 | |a Myeloid Differentiation Factor 88 |2 NLM | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM | |
| 650 | 7 | |a Nlrp3 protein, mouse |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a ST2825 |2 NLM | |
| 650 | 7 | |a Spiro Compounds |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 650 | 7 | |a Caspase 1 |2 NLM | |
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| 700 | 1 | |a Liu, Man |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Dong-Ni |e verfasserin |4 aut | |
| 700 | 1 | |a Shang, Yu-Fu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yue-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Du, Guan-Hua |e verfasserin |4 aut | |
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