Cell type-specific interleukin-1β signaling in the CNS
Cell type-specific interleukin-1β signaling in the CNS
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DOI：
10.1523/jneurosci.5712-03.2004
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发表时间：
2004-07-21
影响因子：
5.3
通讯作者：
Friedman, W
中科院分区：
文献类型：
--
作者：
Srinivasan, D;Yen, JH;Friedman, W
白细胞介素-1β (IL-1beta) 是一种有效的多效性炎症细胞因子，在损伤、疾病或应激条件下，中枢神经系统中会大量产生。这种细胞因子作用于中枢神经系统神经胶质细胞，从而影响炎症反应，部分通过激活核因子-kappaB (NF-kappaB) 转录因子介导，并随后诱导多种细胞因子。海马中的神经元和星形胶质细胞也表达 1 型 IL-1 受体，表明这种细胞因子可以直接影响神经元功能，但 IL-1β 不会像神经胶质细胞那样诱导神经元产生细胞因子。相反，IL-1β 调节海马神经元的突触功能。在这里，我们证明与星形胶质细胞相比，不同的信号通路介导神经元中 IL-1β 的作用。 IL-1beta 激活 p38 丝裂原激活蛋白激酶 (MAPK) 信号通路，并诱导海马神经元中 CREB 的激活，与海马星形胶质细胞中 NF-kappaB 的激活相反，这表明大脑中细胞类型特异性对 IL-1 的信号反应，并产生不同的功能反应。
Interleukin-1beta(IL-1beta) is a potent and pleiotropic inflammatory cytokine that is highly produced in the CNS under conditions of damage, disease, or stress. This cytokine acts on CNS glia to effect inflammatory responses, mediated in part via activation of the nuclear factor-kappaB (NF-kappaB) transcription factor, and consequent induction of numerous cytokines. Neurons as well as astrocytes in the hippocampus also express the type 1 IL-1 receptor, indicating that this cytokine can influence neuronal function directly, yet IL-1beta does not induce production of cytokines in neurons as it does in glia. In contrast, IL-1beta regulates synaptic function of hippocampal neurons. Here we demonstrate that different signaling pathways mediate IL-1beta actions in neurons as compared with astrocytes. IL-1beta activates the p38 mitogen-activated protein kinase ( MAPK) signaling pathway and induces the activation of CREB in hippocampal neurons, in contrast to the activation of NF-kappaB in hippocampal astrocytes, demonstrating cell type-specific signaling responses to IL-1 in the brain and yielding distinct functional responses.