Tukhovskaya Elena A, Turovsky Egor A, Turovskaya Maria V, Levin Sergei G, Murashev Arkady N, Zinchenko Valery P, Godukhin Oleg V
Branch of Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of Russian Academy of Sciences, Pushchino, Russia.
Institute of Cell Biophysics of Russian Academy of Sciences, Pushchino, Russia.
Neurosci Lett. 2014 Jun 13;571:55-60. doi: 10.1016/j.neulet.2014.04.046. Epub 2014 May 4.
It is suggested that anti-inflammatory cytokine interleukin-10 (IL-10) mediates the delayed protective effects through activation of Jak-Stat3, PI3K-Akt and NF-κB signaling pathways. However, our previous experiments have demonstrated that IL-10 is capable to exert the rapid neuroprotective action through modulation of hypoxia-induced intracellular Ca(2+) ([Ca(2+)]i) response. The first purpose of the present study was to evaluate the neuroprotective effects of IL-10 using three models of the ischemic insults in rats: permanent middle cerebral artery occlusion, ischemia in acute hippocampal slices in vitro and ischemia in cultured hippocampal cells in vitro. The second purpose of the study was to elucidate a role of [Ca(2+)]i changes in the mechanisms underlying IL-10 elicited protection of neurons and astrocytes from ischemia-induced death in cultures of primary hippocampal cells. The data presented here shown that anti-inflammatory cytokine IL-10 is capable to induce a resistance of the brain cells to ischemia-evoked damages in in vivo and in vitro models of the ischemic insults in rats. This protective effect in cultured hippocampal cells is developed rapidly after application of IL-10 and strongly associated with the IL-10 elicited elimination of [Ca(2+)]i response to ischemia. Thus, our results provide the evidence that anti-inflammatory cytokine IL-10, in addition to an activation of the canonical signaling pathways, is capable to exert the rapid neuroprotective effects through transcription-independent modulation of ischemia-induced intracellular Ca(2+) responses in the brain cells.
有人认为，抗炎细胞因子白细胞介素-10（IL-10）通过激活Jak-Stat3、PI3K-Akt和NF-κB信号通路介导延迟性保护作用。然而，我们之前的实验表明，IL-10能够通过调节缺氧诱导的细胞内Ca(2+)（[Ca(2+)]i）反应发挥快速的神经保护作用。本研究的第一个目的是使用三种大鼠缺血性损伤模型评估IL-10的神经保护作用：永久性大脑中动脉闭塞、急性海马脑片体外缺血和培养的海马细胞体外缺血。该研究的第二个目的是阐明[Ca(2+)]i变化在IL-10诱导的原代海马细胞培养物中神经元和星形胶质细胞免受缺血性死亡保护机制中的作用。此处呈现的数据表明，抗炎细胞因子IL-10能够在大鼠缺血性损伤的体内和体外模型中诱导脑细胞对缺血性损伤产生抗性。在应用IL-10后，培养的海马细胞中的这种保护作用迅速产生，并且与IL-10诱导的对缺血的[Ca(2+)]i反应消除密切相关。因此，我们的结果提供了证据，表明抗炎细胞因子IL-10除了激活经典信号通路外，还能够通过对脑细胞缺血诱导的细胞内Ca(2+)反应进行转录非依赖性调节来发挥快速的神经保护作用。
