Up-regulated CD38 by daphnetin alleviates lipopolysaccharide-induced lung injury via inhibiting MAPK/NF-κB/NLRP3 pathway
Abstract Background Sepsis is a life-threatening organ dysfunction syndrome resulted from severe infection with high morbidity and mortality. Cluster of differentiation 38 (CD38) is a multifunctional type II transmembrane glycoprotein widely expressed on the surface of various immunocytes membranes...
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| Format: | Article |
| Language: | English |
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BMC
2023-03-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-023-01041-3 |
| _version_ | 1827974427828027392 |
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| author | Yujie Guo Huiqing Zhang Zhe Lv Yuna Du Dan Li Hui Fang Jing You Lijun Yu Rong Li |
| author_facet | Yujie Guo Huiqing Zhang Zhe Lv Yuna Du Dan Li Hui Fang Jing You Lijun Yu Rong Li |
| author_sort | Yujie Guo |
| collection | DOAJ |
| description | Abstract Background Sepsis is a life-threatening organ dysfunction syndrome resulted from severe infection with high morbidity and mortality. Cluster of differentiation 38 (CD38) is a multifunctional type II transmembrane glycoprotein widely expressed on the surface of various immunocytes membranes that mediates host immune response to infection and plays an important role in many inflammatory diseases. Daphnetin (Daph), isolated from the daphne genus plant, is a natural coumarin derivative that possesses anti-inflammatory and anti-apoptotic effects. The current study aimed to investigate the role and mechanism of Daph in alleviating lipopolysaccharide (LPS)-induced septic lung injury, and to explore whether the protective effect of Daph in mice and cell models was related to CD38. Methods Firstly, network pharmacology analysis of Daph was performed. Secondly, LPS-induced septic lung injury in mice were treated with Daph or vehicle control respectively and then assessed for survival, pulmonary inflammation and pathological changes. Lastly, Mouse lung epithelial cells (MLE-12 cells) were transfected with CD38 shRNA plasmid or CD38 overexpressed plasmid, followed by LPS and Daph treatment. Cells were assessed for viability and transfection efficiency, inflammatory and signaling. Results Our results indicated that Daph treatment improved survival rate and alleviated pulmonary pathological damage of the sepsis mice, as well as reduced the excessive release of pro-inflammatory cytokines IL-1β, IL-18, IL-6, iNOS and chemokines MCP-1 regulated by MAPK/NF-κB pathway in pulmonary injury. Daph treatment decreased Caspase-3 and Bax, increased Bcl-2, inhibited nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome‐mediated pyroptosis in lung tissues of septic lung injury. Also, Daph treatment reduced the level of excessive inflammatory mediators, inhibited apoptosis and pyroptosis in MLE-12 cells. It is noteworthy that the protective effect of Daph on MLE-12 cells damage and death was assisted by the enhanced expression of CD38. Conclusions Our results demonstrated that Daph offered a beneficial therapeutic effect for septic lung injury via the up-regulation of CD38 and inhibition of MAPK/NF-κB/NLRP3 pathway. Video Abstract |
| first_indexed | 2024-04-09T19:54:11Z |
| format | Article |
| id | doaj.art-6cc46988558a406692ded42530403bfd |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-09T19:54:11Z |
| publishDate | 2023-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-6cc46988558a406692ded42530403bfd2023-04-03T05:34:29ZengBMCCell Communication and Signaling1478-811X2023-03-0121112410.1186/s12964-023-01041-3Up-regulated CD38 by daphnetin alleviates lipopolysaccharide-induced lung injury via inhibiting MAPK/NF-κB/NLRP3 pathwayYujie Guo0Huiqing Zhang1Zhe Lv2Yuna Du3Dan Li4Hui Fang5Jing You6Lijun Yu7Rong Li8Department of Clinical Laboratory, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical CollegeDepartment of Clinical Laboratory, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical CollegeDepartment of Clinical Laboratory, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical CollegeDepartment of Clinical Laboratory, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical CollegeDepartment of Clinical Laboratory, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical CollegeDepartment of Clinical Laboratory, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical CollegeDepartment of Clinical Laboratory, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical CollegeDepartment of Clinical Laboratory, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical CollegeDepartment of Clinical Laboratory, Jiangxi Provincial People’s Hospital and The First Affiliated Hospital of Nanchang Medical CollegeAbstract Background Sepsis is a life-threatening organ dysfunction syndrome resulted from severe infection with high morbidity and mortality. Cluster of differentiation 38 (CD38) is a multifunctional type II transmembrane glycoprotein widely expressed on the surface of various immunocytes membranes that mediates host immune response to infection and plays an important role in many inflammatory diseases. Daphnetin (Daph), isolated from the daphne genus plant, is a natural coumarin derivative that possesses anti-inflammatory and anti-apoptotic effects. The current study aimed to investigate the role and mechanism of Daph in alleviating lipopolysaccharide (LPS)-induced septic lung injury, and to explore whether the protective effect of Daph in mice and cell models was related to CD38. Methods Firstly, network pharmacology analysis of Daph was performed. Secondly, LPS-induced septic lung injury in mice were treated with Daph or vehicle control respectively and then assessed for survival, pulmonary inflammation and pathological changes. Lastly, Mouse lung epithelial cells (MLE-12 cells) were transfected with CD38 shRNA plasmid or CD38 overexpressed plasmid, followed by LPS and Daph treatment. Cells were assessed for viability and transfection efficiency, inflammatory and signaling. Results Our results indicated that Daph treatment improved survival rate and alleviated pulmonary pathological damage of the sepsis mice, as well as reduced the excessive release of pro-inflammatory cytokines IL-1β, IL-18, IL-6, iNOS and chemokines MCP-1 regulated by MAPK/NF-κB pathway in pulmonary injury. Daph treatment decreased Caspase-3 and Bax, increased Bcl-2, inhibited nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome‐mediated pyroptosis in lung tissues of septic lung injury. Also, Daph treatment reduced the level of excessive inflammatory mediators, inhibited apoptosis and pyroptosis in MLE-12 cells. It is noteworthy that the protective effect of Daph on MLE-12 cells damage and death was assisted by the enhanced expression of CD38. Conclusions Our results demonstrated that Daph offered a beneficial therapeutic effect for septic lung injury via the up-regulation of CD38 and inhibition of MAPK/NF-κB/NLRP3 pathway. Video Abstracthttps://doi.org/10.1186/s12964-023-01041-3DaphnetinSepsisLung injuryCD38InflammationPyroptosis |
| spellingShingle | Yujie Guo Huiqing Zhang Zhe Lv Yuna Du Dan Li Hui Fang Jing You Lijun Yu Rong Li Up-regulated CD38 by daphnetin alleviates lipopolysaccharide-induced lung injury via inhibiting MAPK/NF-κB/NLRP3 pathway Cell Communication and Signaling Daphnetin Sepsis Lung injury CD38 Inflammation Pyroptosis |
| title | Up-regulated CD38 by daphnetin alleviates lipopolysaccharide-induced lung injury via inhibiting MAPK/NF-κB/NLRP3 pathway |
| title_full | Up-regulated CD38 by daphnetin alleviates lipopolysaccharide-induced lung injury via inhibiting MAPK/NF-κB/NLRP3 pathway |
| title_fullStr | Up-regulated CD38 by daphnetin alleviates lipopolysaccharide-induced lung injury via inhibiting MAPK/NF-κB/NLRP3 pathway |
| title_full_unstemmed | Up-regulated CD38 by daphnetin alleviates lipopolysaccharide-induced lung injury via inhibiting MAPK/NF-κB/NLRP3 pathway |
| title_short | Up-regulated CD38 by daphnetin alleviates lipopolysaccharide-induced lung injury via inhibiting MAPK/NF-κB/NLRP3 pathway |
| title_sort | up regulated cd38 by daphnetin alleviates lipopolysaccharide induced lung injury via inhibiting mapk nf κb nlrp3 pathway |
| topic | Daphnetin Sepsis Lung injury CD38 Inflammation Pyroptosis |
| url | https://doi.org/10.1186/s12964-023-01041-3 |
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