Glia maturation factor regulation of STAT expression: a novel mechanism in experimental autoimmune encephalomyelitis.
Glia maturation factor regulation of STAT expression: a novel mechanism in experimental autoimmune encephalomyelitis.
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胶质细胞成熟因子对 STAT 表达的调节：实验性自身免疫性脑脊髓炎的一种新机制。
DOI：
10.1007/s11064-007-9383-0
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发表时间：
2007
影响因子：
4.4
通讯作者：
Zaheer,Asgar
中科院分区：
文献类型：
--
作者：
Zaheer,Smita;Wu,Yanghong;Bassett,Jon;Yang,Baoli;Zaheer,Asgar
炎症细胞因子参与实验性自身免疫性脑脊髓炎（EAE）（一种多发性硬化症动物模型）的发病机制。我们之前证明，神经胶质成熟因子（GMF）是一种在我们实验室中分离、测序和克隆的脑蛋白，可诱导中枢神经系统（CNS）中促炎细胞因子/趋化因子的表达。我们发现，GMF 缺陷（基因敲除）小鼠在使用致脑炎 MOG 肽 35-55 免疫后，对 EAE 的发展具有相对抵抗力。与这些发现一致的是，EAE 小鼠 CNS 中促炎细胞因子的表达在野生型和 GMF 敲除小鼠之间存在显着差异。在本研究中，我们检查了六种小鼠信号转导子和转录激活子（STAT）基因的表达，这些基因已知在自身免疫炎症中调节细胞因子依赖性信号转导途径。通过定量实时 RT-PCR 评估了野生型和 GMF 敲除小鼠在 EAE 高峰期的大脑和脊髓中 STATs 基因的表达。与GMF敲除小鼠相比，表现出EAE症状的野生型小鼠中STAT1、STAT2、STAT3、STAT4、STAT5和STAT6基因的表达显着上调（P<0.001）。结果与 GMF 敲除小鼠中 EAE 发展减弱的情况一致。 GMF 敲除小鼠中 STATs 表达的显着抑制表明 GMF 是 JAK/STAT 信号传导的上游效应子。
Inflammatory cytokines are implemented in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We previously demonstrated that glia maturation factor (GMF), a brain protein, isolated, sequenced and cloned in our laboratory, induce expression of proinflammatory cytokine/chemokine in the central nervous system (CNS). We found GMF-deficient (knockout) mice relatively resistant to EAE development after immunization with encephalitogenic MOG peptide 35–55. Consistent with these findings, the expression of proinflammatory cytokines in CNS of mice with EAE differed profoundly between wild type and GMF-knockout mice. In the present study we examined the expressions of six murine signal transducers and activators of transcription (STATs) genes, which are known to regulate the cytokine-dependent signal transduction pathways in autoimmune inflammation. The expressions of STATs genes were evaluated in the brains and spinal cords of wild type and GMF-knockout mice at the peak of EAE by quantitative real-time RT-PCR. Compared to GMF-knockout mice, the expressions of STAT1, STAT2, STAT3, STAT4, STAT5, and STAT6 genes were significantly (P< 0.001) upregulated in the wild type mice exhibiting EAE symptoms. The results are consistent with the diminished development of EAE in the GMF-knockout mice. A significant suppression of STATs expression in GMF-knockout mice suggests GMF as an upstream effector of JAK/STAT signaling.