Department of Physiology, School of Medicine, Nantong University, Nantong, China.
Int J Neurosci. 2011 Aug;121(8):423-9. doi: 10.3109/00207454.2011.556280.
A mechanism for neuroprotection of interleukin-6 (IL-6) via reduction of intracellular Ca2+ overload induced by N-methyl-D-aspartate (NMDA) was explored. Cerebellar granule neurons (CGNs) from postnatal 8-day infant rats were chronically exposed to IL-6 for 8 days. Confocal laser scanning microscope was used to measure dynamic changes of intracellular Ca2+ fluorescence intensity. NMDA triggered an acute and sustaining enhancement of intracellular Ca2+ fluorescence intensity in the cultured CGNs, whereas NMDA stimulation of the neurons that had been exposed to IL-6 reduced the intracellular Ca2+ fluorescence intensity relative to that of non-IL-6-pretreated neurons. Ethylene glycol bis(aminoethylether) tetraacetate (EGTA), a chelator of extracellular Ca2+, decreased the intracellular Ca2+ overload triggered by NMDA. The component of intracellular Ca2+ overload after EGTA treatment was prevented by IL-6 chronic exposure. Cotreatment with dantrolene sodium (DAN) and 2-aminoethoxydiphenylborate (2-APB), blockers of ryanodine receptor (RyR) and inositol 1,4,5-trisphosphate receptor (IP3R), respectively, also decreased the intracellular Ca2+ overload triggered by NMDA. However, the component of intracellular Ca2+ overload after DAN and 2-APB treatment was only slightly but not significantly diminished by IL-6. These results suggest that IL-6 has a neuroprotective effect against NMDA-induced intracellular Ca2+ overload, and that the effect is implemented primarily via a suppression of Ca2+ release from the intracellular Ca2+ store.
探讨了白细胞介素 6（IL-6）通过减少 N-甲基-D-天冬氨酸（NMDA）诱导的细胞内 Ca2+超载来实现神经保护的机制。将来自出生后 8 天的幼鼠的小脑颗粒神经元（CGN）长期暴露于 IL-6 8 天。使用共聚焦激光扫描显微镜测量细胞内 Ca2+荧光强度的动态变化。NMDA 引发培养的 CGN 中细胞内 Ca2+荧光强度的急性和持续增强，而 NMDA 刺激已经暴露于 IL-6 的神经元导致细胞内 Ca2+荧光强度相对于未经 IL-6 预处理的神经元降低。乙二胺四乙酸（EGTA），一种细胞外 Ca2+螯合剂，降低了 NMDA 引发的细胞内 Ca2+超载。IL-6 慢性暴露可防止 EGTA 处理后的细胞内 Ca2+超载成分。同时使用丹曲林钠（DAN）和 2-氨基乙氧基二苯硼酸盐（2-APB），分别为肌浆网 Ca2+释放通道（RyR）和肌醇 1,4,5-三磷酸受体（IP3R）的阻断剂，也降低了 NMDA 引发的细胞内 Ca2+超载。然而，DAN 和 2-APB 处理后的细胞内 Ca2+超载成分仅略有但无统计学意义地被 IL-6 减少。这些结果表明，IL-6 对 NMDA 诱导的细胞内 Ca2+超载具有神经保护作用，并且该作用主要通过抑制细胞内 Ca2+库的 Ca2+释放来实现。
