Blocking ion channel KCNN4 alleviates the symptoms of experimental autoimmune encephalomyelitis in mice. Academic Article uri icon

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.

published proceedings

  • Eur J Immunol

altmetric score

  • 3

author list (cited authors)

  • Reich, E., Cui, L., Yang, L., Pugliese-Sivo, C., Golovko, A., Petro, M., ... Chou, C.

citation count

  • 70

complete list of authors

  • Reich, Eva-Pia||Cui, Long||Yang, Lily||Pugliese-Sivo, Catherine||Golovko, Andrei||Petro, Mary||Vassileva, Galya||Chu, Inhou||Nomeir, Amin A||Zhang, Li-Kang||Liang, Xian||Kozlowski, Joseph A||Narula, Satwant K||Zavodny, Paul J||Chou, Chuan-Chu

publication date

  • April 2005

publisher