Chrysomycin A Attenuates Neuroinflammation by Down-Regulating NLRP3/Cleaved Caspase-1 Signaling Pathway in LPS-Stimulated Mice and BV2 Cells
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 invest...
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| author | Man Liu Shan-Shan Zhang Dong-Ni Liu Ying-Lin Yang Yue-Hua Wang Guan-Hua Du |
| author_facet | Man Liu Shan-Shan Zhang Dong-Ni Liu Ying-Lin Yang Yue-Hua Wang Guan-Hua Du |
| author_sort | Man Liu |
| collection | DOAJ |
| description | 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. |
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| spelling | doaj.art-fc7ac955104b4f38ad4a68d4ebf01be82023-11-22T01:35:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213679910.3390/ijms22136799Chrysomycin A Attenuates Neuroinflammation by Down-Regulating NLRP3/Cleaved Caspase-1 Signaling Pathway in LPS-Stimulated Mice and BV2 CellsMan Liu0Shan-Shan Zhang1Dong-Ni Liu2Ying-Lin Yang3Yue-Hua Wang4Guan-Hua Du5State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, ChinaChrysomycin 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.https://www.mdpi.com/1422-0067/22/13/6799Chrysomycin AneuroinflammationBV2 microglia cellslipopolysaccharide (LPS) |
| spellingShingle | Man Liu Shan-Shan Zhang Dong-Ni Liu Ying-Lin Yang Yue-Hua Wang Guan-Hua Du Chrysomycin A Attenuates Neuroinflammation by Down-Regulating NLRP3/Cleaved Caspase-1 Signaling Pathway in LPS-Stimulated Mice and BV2 Cells International Journal of Molecular Sciences Chrysomycin A neuroinflammation BV2 microglia cells lipopolysaccharide (LPS) |
| title | Chrysomycin A Attenuates Neuroinflammation by Down-Regulating NLRP3/Cleaved Caspase-1 Signaling Pathway in LPS-Stimulated Mice and BV2 Cells |
| title_full | Chrysomycin A Attenuates Neuroinflammation by Down-Regulating NLRP3/Cleaved Caspase-1 Signaling Pathway in LPS-Stimulated Mice and BV2 Cells |
| title_fullStr | Chrysomycin A Attenuates Neuroinflammation by Down-Regulating NLRP3/Cleaved Caspase-1 Signaling Pathway in LPS-Stimulated Mice and BV2 Cells |
| title_full_unstemmed | Chrysomycin A Attenuates Neuroinflammation by Down-Regulating NLRP3/Cleaved Caspase-1 Signaling Pathway in LPS-Stimulated Mice and BV2 Cells |
| title_short | Chrysomycin A Attenuates Neuroinflammation by Down-Regulating NLRP3/Cleaved Caspase-1 Signaling Pathway in LPS-Stimulated Mice and BV2 Cells |
| title_sort | chrysomycin a attenuates neuroinflammation by down regulating nlrp3 cleaved caspase 1 signaling pathway in lps stimulated mice and bv2 cells |
| topic | Chrysomycin A neuroinflammation BV2 microglia cells lipopolysaccharide (LPS) |
| url | https://www.mdpi.com/1422-0067/22/13/6799 |
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