Back to Search
Start Over
Chrysomycin A Attenuates Neuroinflammation by Down-Regulating NLRP3/Cleaved Caspase-1 Signaling Pathway in LPS-Stimulated Mice and BV2 Cells.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Jun 24; Vol. 22 (13). Date of Electronic Publication: 2021 Jun 24. - Publication Year :
- 2021
-
Abstract
- Chrysomycin A (Chr-A), an antibiotic chrysomycin, was discovered in 1955 and is used to treat cancer and tuberculosis. In the present study, the anti-neuroinflammatory effects and possible mechanism of Chr-A in BALB/c mice and in BV2 microglia cells stimulated by lipopolysaccharide (LPS) were investigated. Firstly, the cortex tissues of mice were analyzed by RNA-seq transcriptome to identify differentially expressed genes (DEGs) regulated by Chr-A in LPS-stimulated mice. Inflammatory cytokines and inflammatory proteins were detected by enzyme-linked immunosorbent assay and Western blot. In RNAseq detection, 639 differential up-regulated genes between the control group and LPS model group and 113 differential down-regulated genes between the LPS model group and Chr-A treatment group were found, and 70 overlapping genes were identified as key genes for Chr-A against neuroinflammation. Subsequent GO biological process enrichment analysis showed that the anti-neuroinflammatory effect of Chr-A might be related to the response to cytokine, cellular response to cytokine stimulus, and regulation of immune system process. The significant signaling pathways of KEGG enrichment analysis were mainly involved in TNF signaling pathway, cytokine-cytokine receptor interaction, NF-κB signaling pathway, IL-17 signaling pathway and NOD-like receptor signaling pathway. Our results of in vivo or in vitro experiments showed that the levels of pro-inflammatory factors including NO, IL-6, IL-1β, IL-17, TNF-α, MCP-1, CXCL12, GM-CSF and COX2 in the LPS-stimulated group were higher than those in the control group, while Chr-A reversed those conditions. Furthermore, the Western blot analysis showed that its anti-neuroinflammation appeared to be related to the down-regulation of NLRP3/cleaved caspase-1 signaling pathway. The current findings provide new insights into the activity and molecular mechanisms of Chr-A for the treatment of neuroinflammation.
- Subjects :
- Aminoglycosides chemistry
Animals
Cerebral Cortex drug effects
Cerebral Cortex immunology
Cerebral Cortex metabolism
Cerebral Cortex pathology
Disease Models, Animal
Gene Expression Profiling
Gene Expression Regulation drug effects
Lipopolysaccharides immunology
Mice
Microglia immunology
Molecular Structure
Neurogenic Inflammation etiology
Proteolysis
Transcriptome
Aminoglycosides pharmacology
Caspase 1 metabolism
Microglia drug effects
Microglia metabolism
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Neurogenic Inflammation metabolism
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34202695
- Full Text :
- https://doi.org/10.3390/ijms22136799