Immunosuppressive effects of a Kv1.3 inhibitor |
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Authors: | Shah Kashmira Tom Blake J Huang Christopher Fischer Paul Koo Gloria C |
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Institution: | Merck Research Laboratories, 80W-107, PO Box 2000, Rahway, NJ 07065, USA. |
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Abstract: | The voltage gated potassium channel (Kv1.3) has been shown to play a role in immune responsiveness. Blockade of the channel led to diminution of T cell activation and delayed type hypersensitivity. Previous in vitro studies of the blockade were focused on T cell activation and proliferation. In this study we examined other T and monocytic cell mediated events to glean the extent of the immunosuppressive effects of a Kv1.3 specific inhibitor, Margatoxin (MgTX). We found that MgTX inhibited the intracellular production of Th-1 as well as Th-2 cytokines. MgTX can also inhibit IL-2 production and proliferation of T cells upon stimulation with anti-CD3 and VCAM-1. Furthermore, a redirected cytolytic activity was also inhibited by MgTX. However, MgTX did not inhibit generation of CTL to EBV transformed lymphoma cells or antibody-dependent cellular cytolysis mediated by monocytes. It appears that a Kv1.3 blockade does not affect all immune responses, particularly those of innate immunity. |
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Keywords: | Immunosuppression Kv1 3 Margatoxin VCAM-1 |
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