Liu Zhan, Fang Xiao-Xia, Chen Yu-Ping, Qiu Yi-Hua, Peng Yu-Ping
School of Biological & Basic Medical Sciences, Soochow University, Suzhou, PR China.
Brain Inj. 2013;27(9):1047-55. doi: 10.3109/02699052.2013.794970. Epub 2013 Jun 3.
The mechanism underlying interleukin-6 (IL-6) prevention of N-methyl-D-aspartate (NMDA)-induced neuronal Ca(2+) overload was explored at the profile of Ca(2+) channel receptors, including NMDA, inositol 1,4,5-trisphosphate and ryanodine receptors (NMDAR, IP3R and RyR, respectively).
Cerebellar granule neurons from 8-day-old rats were exposed to IL-6 (40 or 120 ng ml(-1)) for 8 days and stimulated with NMDA (100 μM) for 15 or 30 minutes.
NMDA evoked an acute and sustained enhancement of intracellular Ca(2+) fluorescence intensity in the entire 15-minute NMDA application period. IL-6 prevented the acute and sustained intracellular Ca(2+) elevation triggered by NMDA in a concentration-dependent manner. MK-801, an NMDAR antagonist, completely suppressed NMDA-evoked neuronal Ca(2+) overload in the absence or presence of IL-6. IP3R antagonist 2-APB lessened NMDA-evoked acute and sustained cytosolic Ca(2+) overload and IL-6 further reduced the acute 2-APB-dependent Ca(2+) component. Dissimilarly, after RyR antagonist DAN treatment, NMDA still induced an acute and sustained elevation of intracellular Ca(2+) levels, and the elevated Ca(2+) was significantly suppressed by IL-6. Moreover, IL-6 down-regulated NMDAR1 and IP3R1 but did not alter RyR2 expression.
The present results suggest that IL-6 suppresses NMDA-induced neuronal Ca(2+) overload by inhibiting NMDAR and IP3R activities.
从钙通道受体（包括N-甲基-D-天冬氨酸受体、肌醇1,4,5-三磷酸受体和兰尼碱受体，分别为NMDAR、IP3R和RyR）的层面，探究白细胞介素-6（IL-6）预防N-甲基-D-天冬氨酸（NMDA）诱导的神经元钙（Ca²⁺）超载的潜在机制。
将8日龄大鼠的小脑颗粒神经元暴露于IL-6（40或120 ng/ml）8天，并用NMDA（100 μM）刺激15或30分钟。
在整个15分钟的NMDA应用期间，NMDA引起细胞内Ca²⁺荧光强度急性且持续增强。IL-6以浓度依赖的方式预防了NMDA触发的细胞内Ca²⁺急性和持续升高。NMDAR拮抗剂MK-801在不存在或存在IL-6的情况下，完全抑制了NMDA诱发的神经元Ca²⁺超载。IP3R拮抗剂2-APB减轻了NMDA诱发的急性和持续的胞质Ca²⁺超载，而IL-6进一步降低了急性2-APB依赖性Ca²⁺成分。不同的是，在RyR拮抗剂DAN处理后，NMDA仍诱导细胞内Ca²⁺水平急性和持续升高，而IL-6显著抑制了升高的Ca²⁺。此外，IL-6下调了NMDAR1和IP3R1，但未改变RyR2的表达。
目前的结果表明，IL-6通过抑制NMDAR和IP3R活性来抑制NMDA诱导的神经元Ca²⁺超载。
