Immunosuppressive effects of a Kv1.3 inhibitor.
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.
Shah
Kashmira
K
Merck Research Laboratories, 80W-107, PO Box 2000, Rahway, NJ 07065, USA.
Tom Blake
J
J
Huang
Christopher
C
Fischer
Paul
P
Koo
Gloria C
GC
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects / Q000276:immunology; D015759:Ionomycin / Q000276:immunology / Q000494:pharmacology; D007476:Ionophores / Q000276:immunology / Q000494:pharmacology; D051664:Kv1.3 Potassium Channel; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D009498:Neurotoxins / Q000276:immunology / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000276:immunology / Q000494:pharmacology*; D015221:Potassium Channels / Q000276:immunology* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology / Q000494:pharmacology
D016207:Cytokines; D007166:Immunosuppressive Agents; D007476:Ionophores; C496973:KCNA3 protein, human; D051664:Kv1.3 Potassium Channel; D009498:Neurotoxins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; D015759:Ionomycin; C077910:margatoxin; D013755:Tetradecanoylphorbol Acetate