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首页> 外文期刊>Cellular immunology >Immune response in the relapsing-remitting experimental autoimmune encephalomyelitis in mice: The role of the NF-kappa B signaling pathway
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Immune response in the relapsing-remitting experimental autoimmune encephalomyelitis in mice: The role of the NF-kappa B signaling pathway

机译:在小鼠中复发储存实验性自身免疫脑膜炎术中的免疫反应:NF-Kappa发信息途径的作用

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Characteristics of the mouse model of relapsing-remitting experimental autoimmune encephalomyelitis (rEAE) closely resemble manifestations of multiple sclerosis in humans. In the present study, we investigated the mechanisms of inflammatory response, focusing on NF-kappa B pathway activation. Cytokine response in rEAE mice was multiphasic: the early phase was characterized by the increase in interferon-gamma level in plasma. In the later stage, the level of interleukin-17, but not of interferon-gamma, was increased. The early phase of rEAE was also accompanied by increased RelA/p65 phosphorylation at Ser276 in spleen cells, whereas the rEAE maintenance phase was characterized by RelA/p65 phosphorylation at Ser536 and IKK phosphorylation. The IKK alpha/beta inhibitor reduced interleukin-17 and interferon-y levels in plasma and alleviated rEAE symptoms. The IKK alpha/beta inhibitor decreased IKK and p65(Ser536) phosphorylation, but doubled p65(Ser276) phosphorylation in rEAE mice. The increased RelA/p65(Ser276) phosphorylation coincided in time with the production of interferon-gamma, Hsp72, and the early phase of IL-17 generation, whereas increased RelA/p65(Ser536) phosphorylation coincided with the activation of IKK, SAPK/JNK, and p53, as well as the late phase of IL-17 production, indicating the role of the RelA/p65 phosphorylation events in the induction and maintenance of rEAE.
机译:复发式实验性自身免疫脑脊髓炎(REAE)的鼠标模型特征与人类多发性硬化的表现相似。在本研究中,我们研究了炎症反应的机制,重点是NF-Kappa途径激活。 Reae小鼠中的细胞因子反应是多相的:早期阶段的特征在于血浆中干扰素-γ水平的增加。在后期,白细胞介素-17的水平,但不具有干扰素-γ的水平。 REAE的早期阶段也伴随于脾细胞SER276的REARA / P65磷酸化,而RES / P65在SER536和IKK磷酸化上的磷酸化表征了REAE维持阶段。 IKKα/β抑制剂在血浆中减少白细胞介素-17和干扰素-Y水平,缓解了症状。 IKKα/β抑制剂降低IKK和P65(SER536)磷酸化,但在REEE小鼠中加倍P65(Ser276)磷酸化。随着Interon-gamma,Hsp72和IL-17代早期的产生,Rela / P65(Ser276)磷酸化恰好恰好,而Rela / P65(Ser536)磷酸化与IKK,SAPK的激活相吻合。 JNK和P53,以及IL-17生产的后期,表明Rela / P65磷酸化事件在诱导和维持的磷酸化事件中的作用。

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