Back to Search
Start Over
Immunosuppressive effects of triptolide via interleukin-2/receptor signaling.
- Source :
-
Immunopharmacology & Immunotoxicology . Sep2024, p1-14. 14p. 6 Illustrations. - Publication Year :
- 2024
-
Abstract
- AbstractBackgroundObjectiveMethodsResultsConclusionsTriptolide (TP) has been confirmed to possess many beneficial functions including anti-inflammation and immunosuppression.The present study aimed to explore the potential involvement of IL-2/IL-2R pathway in the immunosuppressive activities of TP.Cultured CTLL-2 cells were utilized to evaluate the potential benefits of TP. Then cell viability was determined by CCK-8 assay, IFN-γ level by ELISA assay, Annexin V-FITC/PI double-staining and CD25 expression by flow cytometry, and protein expression by western blotting. Additionally, rhIL-2–driven lymphocytes following ConA activation were investigated. The interactions of TP with IL-2 and IL-2Rα were investigated by binding assays and molecular dynamics simulations.TP treatment attenuated IFN-γ level and cell viability in both rhIL-2–induced CTLL-2 cells and rhIL-2–driven splenic lymphocytes. TP treatment increased cellular apoptosis/necrosis and cleaved PARP-1 level, while suppressed c-Myc level in rhIL-2–induced CTLL-2 cells. Additionally, TP treatment reduced CD25 expression on CTLL-2 cell surface. Notably, the phosphorylation protein levels in IL-2R signaling pathways were inhibited by TP exposure prior to rhIL-2 stimulation. SPR and BLI assays verified TP that directly bound to rhIL-2 and rmIL-2Rα, respectively. Molecular simulations suggested that TP bound at the interface of IL-2 and IL-2Rα near the hydrophobic patch composed of F62, L92 on IL-2 and L23, I46, V139 on IL-2Rα, resulting in decreased binding free energy between IL-2 and IL-2Rα.These findings collectively emphasized that TP interfered IL-2/IL-2Rα interactions, down-regulated IL-2Rα expression, and inhibited IL-2R signaling pathways activation, thereby leading to the immune cells being desensitized to rhIL-2 and exhibiting immunosuppressive properties. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08923973
- Database :
- Academic Search Index
- Journal :
- Immunopharmacology & Immunotoxicology
- Publication Type :
- Academic Journal
- Accession number :
- 179731385
- Full Text :
- https://doi.org/10.1080/08923973.2024.2373219