Interleukin-1β protects neurons via the interleukin-1 (IL-1) receptor-mediated Akt pathway and by IL-1 receptor-independent decrease of transmembrane currents in vivo
Interleukin-1β protects neurons via the interleukin-1 (IL-1) receptor-mediated Akt pathway and by IL-1 receptor-independent decrease of transmembrane currents in vivo
复制标题
DOI：
10.1016/s1044-7431(02)00042-8
复制
发表时间：
2003-04-01
影响因子：
3.5
通讯作者：
Bähr, M
中科院分区：
文献类型：
--
作者：
Diem, R;Hobom, M;Bähr, M
最近我们已经证明了肿瘤坏死因子-α（TNF-α）在视神经轴突切断术后挽救视网膜神经节细胞（RGC）免于体内逆行性细胞死亡。RGC的拯救机制依赖于TNF-受体I介导的钾电流减少和磷脂酰肌醇3-激酶（PI 3-K）/Akt通路的连续激活。在这里，我们提出了白细胞介素-1 β（IL-1 β）也促进RGC存活的证据，但在其神经保护机制方面表现出明显的差异。采用全细胞膜片钳和外向膜片钳技术，我们观察到IL-1 β降低内向钠电流和外向钾电流的幅度。通过钠或钾通道开放抵消这些作用抑制了这种细胞因子的生存促进作用。IL-1 β诱导的电流降低不能被白细胞介素-1受体拮抗剂消除，表明IL-1 β的电生理效应不依赖于白细胞介素-1受体I（IL-1 RI）的激活。Western blot分析显示IL-1 β诱导的IL-1 RI依赖性磷酸化Akt上调。PI 3-K抑制对IL-1 β促存活作用的拮抗作用揭示了体内IL-1 β诱导的信号转导中PI 3-K/Akt通路的功能相关性。(C)2003 Elsevier Science（美国）。All rights reserved.
Recently. we have demonstrated that tumor necrosis factor-alpha (TNF-alpha) rescues retinal ganglion cells (RGCs) from retrograde cell death in vivo after axotomy of the optic nerve. The mechanism of RGC rescue was dependent on TNF-receptor I-mediated potassium current reduction and consecutive activation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. Here, we present evidence that interleukin-1beta (IL-1beta) also promotes RGC survival, but shows distinct differences with respect to its neuroprotective mechanisms. Using whole-cell and outside-out patch-clamp techniques, we observed that IL-1beta decreased both inward sodium current amplitudes and outward potassium current amplitudes. Counteracting these effects by sodium or potassium channel opening inhibited the survival-promoting effects of this cytokine. IL-1beta-induced current reduction could not be abolished by the interleukin-1 receptor antagonist, indicating that the electrophysiological effects of IL-1beta are independent of interleukin-1 receptor I (IL-1RI) activation. Western blot analysis revealed an IL-1beta-induced IL-1RI-dependent Upregulation of phospho-Akt. Antagonism of the survival-promoting effects of IL-1beta by PI3-K inhibition revealed the functional relevance of the PI3-K/Akt pathway in IL-1beta-induced signal transduction in vivo. (C) 2003 Elsevier Science (USA). All rights reserved.