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Effect of cyclosporine A on the regulation of Ia antigen keratinocytes expression
A Gilhar1, A Etzioni, T Pillar
1Skin Research Laboratory, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
Abstract:
Since many skin diseases characterized by positive Ia keratinocytes show improvement with cyclosporine therapy, the purpose of this study was to determine whether cyclosporine A (CyA) alters the expression of Ia keratinocytes. Nude mice were injected with normal mouse serum (NMS) to induce keratinocyte expression of the Ia antigen. The injected mice were then divided into four groups: one was treated with oral CyA; the second was treated topically with CyA twice a day; the third was treated topically with olive oil; and the fourth was injected with nude mouse serum. The third and fourth groups served as Ia positive and Ia negative controls, respectively. The mice were treated during the first 10 days after the injections. On Day 10, epidermal sheets were analyzed for Ia expression. Analysis was made by an indirect immunoperoxidase staining method using monoclonal antibodies specific for Ia determinants. Quantitation of the number of Langerhans cells was analyzed on epidermal sheets using immunodiagnostic reagents, anti-MHC-Ia, and surface ectoenzyme, ATPase. A significant reduction of Ia-positive keratinocytes was noted in the oral CyA group vs topical and olive oil groups (64.9 +/- 29.9% vs 20.1 +/- 18.7%, respectively, P less than 0.01). In a second set of experiments mice were injected with NMS, but treatment was started only on Day 10 after injections, for 10 days. The results showed that CyA failed to down-regulate Ia expression. Topical and systemic CyA did not modify Langerhans cell population. The present study showed that systemic administration of CyA significantly reduced Ia induction by keratinocytes of nude mice that were injected with NMS.
Insights
Systemic cyclosporine A (CyA) significantly reduced Ia antigen expression in keratinocytes of nude mice. However, CyA did not affect Langerhans cell populations or down-regulate Ia expression when treatment began after induction.
Area of Science:
- Immunodermatology
- Cell Biology
- Pharmacology
Background:
- Many skin diseases with positive Ia keratinocytes improve with cyclosporine therapy.
- Cyclosporine A (CyA) is an immunosuppressant used in treating various skin conditions.
- The role of Ia antigen expression in keratinocytes and its modulation by CyA requires further investigation.
Purpose of the Study:
- To investigate whether cyclosporine A (CyA) alters the expression of Ia antigen in keratinocytes.
- To determine the effect of systemic and topical CyA on Ia expression in a mouse model.
Main Methods:
- Nude mice were injected with normal mouse serum (NMS) to induce Ia antigen expression.
- Mice were treated with oral or topical CyA, or olive oil, during the first 10 days post-injection.
- Epidermal sheets were analyzed for Ia expression using immunoperoxidase staining and cell counts.
Main Results:
- Systemic (oral) CyA significantly reduced Ia-positive keratinocytes compared to topical CyA or olive oil controls.
- Delayed treatment with CyA (starting on Day 10) failed to down-regulate established Ia expression.
- Neither topical nor systemic CyA altered the Langerhans cell population.
Conclusions:
- Systemic administration of cyclosporine A can significantly reduce the induction of Ia antigen expression in keratinocytes.
- The timing of CyA administration is crucial for its efficacy in modulating Ia expression.
- CyA does not appear to affect the Langerhans cell population in this model.