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
Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Eur J Immunol. 2005 Apr;35(4):1027-36. doi: 10.1002/eji.200425954.
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.
据报道，KCNN4钾离子通道在体外调节抗原诱导的T细胞效应功能中发挥重要作用。本研究首次证明，选择性KCNN4阻滞剂TRAM-34在小鼠模型中对实验性自身免疫性脑脊髓炎（EAE）具有保护作用。用KCNN4阻滞剂治疗并未阻止T细胞浸润脊髓，但导致脊髓中TNF-α和IFN-γ的蛋白质和信使水平以及其他几种促炎分子的信使水平降低。TRAM-34在24小时内的血浆浓度介于KCNN4通道的体外IC（50）和IC（90）值之间。TRAM-34的作用是可逆的，停药后48小时内出现临床EAE症状即表明了这一点。总之，我们的数据支持这样的观点，即KCNN4通道在C57BL/6小鼠MOG诱导的EAE发展过程中的免疫反应中起关键作用。
