Oligodendrocytes exhibit selective expression of suppressor of cytokine signaling genes and signal transducer and activator of transcription 1 independent inhibition of interferon-gamma-induced toxicity in response to leukemia inhibitory factor
Oligodendrocytes exhibit selective expression of suppressor of cytokine signaling genes and signal transducer and activator of transcription 1 independent inhibition of interferon-gamma-induced toxicity in response to leukemia inhibitory factor
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DOI：
10.1016/j.neuroscience.2005.09.022
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发表时间：
2006-01-01
期刊：
影响因子：
3.3
通讯作者：
Kilpatrick, TJ
中科院分区：
文献类型：
--
作者：
Emery, B;Butzkueven, H;Kilpatrick, TJ
多发性硬化症是一种中枢神经系统的自身免疫性疾病，导致中枢神经系统的髓鞘细胞少突胶质细胞死亡。先前的研究表明，细胞因子白血病抑制因子可以阻止干扰素γ对体外少突胶质细胞的细胞毒性作用，以及多发性硬化症动物模型中少突胶质细胞的死亡。最近发现的一个蛋白质家族的成员，细胞因子信号抑制因子，已经被证明可以介导细胞因子之间的负串扰，通过一个细胞因子抑制另一个细胞因子的活性来诱导细胞因子信号蛋白的抑制因子。在这里，我们评估细胞因子信号家族抑制因子成员的诱导是否可以解释白血病抑制因子和干扰素γ对少突胶质细胞的拮抗生物学效应。研究发现，白血病抑制因子在培养的大鼠少突胶质细胞中能快速、强烈地诱导细胞因子信号通路抑制因子-3的表达，而干扰素γ对细胞因子信号通路抑制因子-1和3的表达均有微弱的诱导作用。用白血病抑制因子预处理少突胶质细胞并不能阻止干扰素- γ随后对信号换能器和转录激活子-1的磷酸化，这表明白血病抑制因子对干扰素- γ毒性的抑制作用是通过细胞因子信号-3抑制因子独立机制介导的。(c) 2005 IBRO。Elsevier Ltd.出版。版权所有。
Multiple sclerosis is an autoimmune disease of the CNS that results in the death of oligodendrocytes, the myelinating cells of the CNS. Previous studies have indicated that the cytokine leukemia inhibitory factor prevents the cytotoxic effects of interferon-gamma on oligodendrocytes in vitro, and the death of oligodendrocytes in an animal model of multiple sclerosis. Members of a recently characterized family of proteins, the suppressors of cytokine signaling, have been demonstrated to mediate negative cross-talk between cytokines, with induction of suppressors of cytokine signaling proteins by one cytokine inhibiting the activity of a second. Here, we assess whether induction of members of the suppressors of cytokine signaling family could explain the antagonistic biological effects of leukemia inhibitory factor and interferon-gamma upon oligodendrocytes. It is found that leukemia inhibitory factor rapidly and strongly induces the expression of suppressors of cytokine signaling-3 in cultured rat oligodendrocytes, whereas interferon-gamma weakly induces the expression of both suppressor of cytokine signaling-1 and 3. Pre-treatment of oligodendrocytes with leukemia inhibitory factor does not prevent the subsequent phosphorylation of signal transducer and activator of transcription-1 by interferon-gamma indicating that the leukemia inhibitory factor inhibition of interferon-gamma toxicity in oligodendrocytes is mediated by a suppressor of cytokine signaling-3 independent mechanism. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.