Blocking ion channel KCNN4 alleviates the symptoms of experimental autoimmune encephalomyelitis in mice.
Eur J Immunol
; 35(4): 1027-36, 2005 Apr.
Article
in En
| MEDLINE
| ID: mdl-15770697
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Potassium Channels, Calcium-Activated
/
Encephalomyelitis, Autoimmune, Experimental
Type of study:
Diagnostic_studies
Limits:
Animals
Language:
En
Journal:
Eur J Immunol
Year:
2005
Document type:
Article
Affiliation country: