Article ; Online: Artesunate protects immunosuppression mice induced by glucocorticoids via enhancing pro-inflammatory cytokines release and bacterial clearance.
European journal of pharmacology
2020 Volume 890, Page(s) 173630
Abstract: ... mice to clear bacteria, but also increased spleen index, the levels of pro-inflammatory cytokines ... immunosuppression was investigated. HC-induced immunosuppression mice (HC mice) were established ... number of white blood cells in blood, and sIgA in colon. Subsequently, HC-induced immunosuppression ...
| Abstract | Glucocorticoids are commonly used in clinic, but the immunosuppression seriously hinders their usage. Herein, immunomodulatory effect of artesunate (AS) on hydrocortisone (HC)-induced immunosuppression was investigated. HC-induced immunosuppression mice (HC mice) were established by intramuscular administration with HC (20 mg/kg) once a day for 5 consecutive days. The results showed HC mice challenged with Escherichia coli on the sixth day presented a lower ability to clear bacteria, decreased TNF-α in blood, decreased spleen index and thymus index. Significantly, AS (20 mg/kg) treatment not only enhanced the ability of HC mice to clear bacteria, but also increased spleen index, the levels of pro-inflammatory cytokines from 78.7 ± 12.1 ng/ml (TNF-α) and 48.7 ± 8.6 pg/ml (IL-6) to 174.0 ± 90.5 ng/ml and 783.3 ± 90.5 pg/ml, number of white blood cells in blood, and sIgA in colon. Subsequently, HC-induced immunosuppression peritoneal macrophages model (HC cells) was established via addition of HC (0.5 μg/ml) for 0.5 h, and then LPS (100 ng/ml) was added to clarify the functional status of the cells. The results showed HC inhibited TNF-α and IL-6 mRNA expressions and their release, but AS (2.5 μg/ml) could increase TNF-α and IL-6 mRNA expressions and their release. AS inhibited GILZ mRNA up-regulated by HC and increases TLR4/NF-κB p65 expressions down-regulated by HC. Our findings revealed that AS's effect is closely related to the improvement of the TLR4/NF-κB signal transduction pathway via inhibiting the up-regulation of GILZ mRNA, demonstrating AS does possess immunomodulatory effects and is worth further investigation in the future. |
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| MeSH term(s) | Animals ; Artesunate/pharmacology ; Artesunate/therapeutic use ; Bacteria/immunology ; Bacterial Load/drug effects ; Cells, Cultured ; Cytokines/drug effects ; Cytokines/metabolism ; Disease Models, Animal ; Glucocorticoids/toxicity ; Immunoglobulin A, Secretory/metabolism ; Immunologic Factors/pharmacology ; Immunologic Factors/therapeutic use ; Immunosuppression Therapy ; Interleukin-6/metabolism ; Leukocytes/drug effects ; Macrophages, Peritoneal/metabolism ; Male ; Mice, Inbred BALB C ; Spleen/drug effects ; Spleen/pathology ; Thymus Gland/drug effects ; Thymus Gland/pathology ; Toll-Like Receptor 4/metabolism ; Transcription Factor RelA/metabolism ; Transcription Factors/metabolism ; Tumor Necrosis Factor-alpha/blood ; Mice | |||||
| Chemical Substances | Cytokines ; Dsip1 protein, mouse ; Glucocorticoids ; Immunoglobulin A, Secretory ; Immunologic Factors ; Interleukin-6 ; Rela protein, mouse ; Tlr4 protein, mouse ; Tnf protein, mouse ; Toll-Like Receptor 4 ; Transcription Factor RelA ; Transcription Factors ; Tumor Necrosis Factor-alpha ; interleukin-6, mouse ; Artesunate (60W3249T9M) | |||||
| Keywords | covid19 | |||||
| Language | English | |||||
| Publishing date | 2020-10-10 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 80121-5 | |||||
| ISSN | 1879-0712 ; 0014-2999 | |||||
| ISSN (online) | 1879-0712 | |||||
| ISSN | 0014-2999 | |||||
| DOI | 10.1016/j.ejphar.2020.173630 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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