Blocking ion channel KCNN4 alleviates the symptoms of experimental autoimmune encephalomyelitis in mice

Autor: Galya Vassileva, Petro Mary E, Long Cui, Inhou Chu, Satwant K. Narula, Andrei Golovko, Lily Yang, Amin A. Nomeir, Catherine Pugliese-Sivo, Paul J. Zavodny, Li-Kang Zhang, Joseph A. Kozlowski, Xian Liang, Chuan-Chu Chou, Eva-Pia Reich
Rok vydání: 2005
Předmět:
Zdroj: European Journal of Immunology. 35:1027-1036
ISSN: 1521-4141
0014-2980
DOI: 10.1002/eji.200425954
Popis: The KCNN4 potassium-ion channel has been reported to play an important role in regulating antigen-induced T cell effector functions in vitro. This study presents the first evidence that a selective KCNN4 blocker, TRAM-34, confers protection against experimental autoimmune encephalomyelitis (EAE) in the mouse model. Treatment with the KCNN4 blocker did not prevent infiltration of T cells in the spinal cord, but resulted in the reduction of both the protein and the message levels of TNF-alpha and IFN-gamma as well as the message levels of several other pro-inflammatory molecules in the spinal cord. Plasma concentrations of TRAM-34 within a 24-h period were between the in vitro IC(50) and IC(90) values for the KCNN4 channel. The effect of TRAM-34 was reversible, as indicated by the development of clinical EAE symptoms within 48 h after withdrawal of treatment. In summary, our data support the idea that KCNN4 channels play a critical role in the immune response during the development of MOG-induced EAE in C57BL/6 mice.
Databáze: OpenAIRE
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