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首页> 外文期刊>Glia >Jagged1 regulates the activation of astrocytes via modulation of NFκB and JAK/STAT/SOCS pathways
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Jagged1 regulates the activation of astrocytes via modulation of NFκB and JAK/STAT/SOCS pathways

机译：Jagged1通过调节NFκB和JAK / STAT / SOCS途径调节星形胶质细胞的激活

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摘要

The Notch pathway is implicated in many aspects of the central nervous system (CNS) development and functions. Recently, we and others identified the Notch pathway to be involved in inflammatory events of the CNS. To understand the implication of this pathway on astrocytes, we have studied the Jagged-Notch-Hes pathway under inflammatory conditions. LPS exposure induced an upregulation of Jagged1 expression on cultured astrocytes. To address the role of Jagged1 in the modulation of inflammation, we used a siRNA mediated silencing of Jagged1 (siRNA J1). Jagged1 inhibition induced important variations on the Notch pathway components like Hes1, Hes5, Notch3, and RBP-Jκ. siRNA J1 repressed the mRNA expression of genes known as hallmarks of the gliosis like GFAP and endothelin(B) receptor. On activated astrocytes, the inhibition of Jagged1 had antiinflammatory effects and resulted in a decrease of LPS-induced proinflammatory cytokines (IL1β, IL1α, and TNFα) as well as the iNOS expression. The inhibition of Jagged1 induced a modulation of the JAK/STAT/SOCS signaling pathway. Most interestingly, the siRNA J1 decreased the LPS-induced translocation of NFκB p65 and this could be correlated to the phosphorylation of IκBα. These results suggest that during inflammatory and gliotic events of the CNS, Jagged1/Notch signaling sustains the inflammation mainly through NFκB and in part through JAK/STAT/SOCS signaling pathways.
机译：Notch通路与中枢神经系统（CNS）的发育和功能的许多方面有关。最近，我们和其他人确定了Notch通路与CNS的炎症事件有关。为了理解该途径对星形胶质细胞的影响，我们研究了炎性条件下的锯齿状缺口Not Hes途径。 LPS暴露诱导培养的星形胶质细胞上Jagged1表达的上调。为了解决Jagged1在炎症调节中的作用，我们使用了siRNA介导的Jagged1沉默（siRNA J1）。 Jagged1抑制诱导Notch通路组件（如Hes1，Hes5，Notch3和RBP-Jκ）的重要变异。 siRNA J1抑制了神经胶质化标志物基因GFAP和内皮素（B）受体的mRNA表达。对活化的星形胶质细胞，Jagged1的抑制具有抗炎作用，并导致LPS诱导的促炎性细胞因子（IL1β，IL1α和TNFα）以及iNOS表达减少。对Jagged1的抑制诱导了JAK / STAT / SOCS信号通路的调节。最有趣的是，siRNA J1降低了LPS诱导的NFκBp65易位，这可能与IκBα的磷酸化有关。这些结果表明，在中枢神经系统的炎症和神经胶质细胞变性事件中，Jagged1 / Notch信号传导主要通过NFκB并部分通过JAK / STAT / SOCS信号传导途径维持炎症。

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