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Glucocorticoids and cyclosporine induce apoptosis in mitogen-activated human peripheral mononuclear cells
1Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Abstract:
Induction of apoptosis by immunosuppressive agents such as glucocorticoids (GCs) and cyclosporine (CsA) in cultured lymphoid cells has been suggested. However, there are few studies which demonstrate the induction of apoptosis by these agents in the activation process of human peripheral blood mononuclear cells (PBMCs). Here we show that potent immunosuppressive GCs and CsA induce apoptosis in concanavalin A (con A)-activated human PBMCs. In this study, GCs and CsA suppressed human PBMC-blastogenesis when activated by con A in a dose-dependent manner, where healthy PBMCs treated with > 100 ng/ml of each immunosuppressive agent exhibited a DNA-ladder structure in electrophoretic analysis. In three chronic renal failure (CRF) patients, dose-dependency of the PBMC-apoptosis induction was confirmed by our quantification of fragmented DNA using ELISA. Furthermore, the enrichment of DNA fragmentation was significantly associated with the rate of PBMC-blastogenesis when treated with GCs or CsA (r = -0.466, P < 0.01). These results suggested that suppression of the mitogen-induced PBMC-blastogenesis by the immunosuppressive agents should be correlated with the induction of apoptosis.
Insights
Glucocorticoids (GCs) and cyclosporine (CsA) induce apoptosis in activated human peripheral blood mononuclear cells (PBMCs). This immunosuppressive effect correlates with reduced PBMC proliferation, suggesting apoptosis as a key mechanism.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Immunosuppressive agents like glucocorticoids (GCs) and cyclosporine (CsA) are known to induce apoptosis in lymphoid cells.
- Limited research exists on apoptosis induction by these agents during the activation of human peripheral blood mononuclear cells (PBMCs).
Purpose of the Study:
- To investigate whether potent immunosuppressive GCs and CsA induce apoptosis in concanavalin A (con A)-activated human PBMCs.
- To explore the relationship between immunosuppressive agent-induced apoptosis and the suppression of PBMC blastogenesis.
Main Methods:
- Human PBMCs were activated with concanavalin A (con A) and treated with varying doses of GCs and CsA.
- PBMC blastogenesis was assessed, and apoptosis was evaluated by DNA-ladder formation via electrophoresis and fragmented DNA quantification using ELISA.
- Correlation analysis was performed between DNA fragmentation and PBMC blastogenesis rates.
Main Results:
- GCs and CsA suppressed con A-induced human PBMC blastogenesis in a dose-dependent manner.
- PBMCs treated with > 100 ng/ml of GCs or CsA exhibited DNA laddering, indicative of apoptosis.
- In chronic renal failure (CRF) patients, dose-dependent apoptosis induction was confirmed, and increased DNA fragmentation significantly correlated with suppressed PBMC blastogenesis (r = -0.466, P < 0.01).
Conclusions:
- Potent immunosuppressive agents, GCs and CsA, effectively induce apoptosis in activated human PBMCs.
- The suppression of mitogen-induced PBMC blastogenesis by these immunosuppressants is strongly correlated with the induction of apoptosis.
- Apoptosis is a key mechanism underlying the immunosuppressive effects of GCs and CsA on activated human PBMCs.