Keratan sulfate expression in microglia is diminished in the spinal cord in experimental autoimmune neuritis.
Keratan sulfate expression in microglia is diminished in the spinal cord in experimental autoimmune neuritis.
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DOI：
10.1038/cddis.2013.479
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发表时间：
2013-12-05
影响因子：
9
通讯作者：
中科院分区：
文献类型：
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实验性自身免疫性神经炎（EAN）是格林-巴利综合征（一种外周神经系统炎性脱髓鞘疾病）的动物模型。虽然这种疾病已经在周围神经上进行了广泛的研究，但中枢神经系统的病理尚未完全了解。以往的研究表明，硫酸角质素（KS），蛋白多糖的糖链的表达，与神经元损伤后积累的活化的小胶质细胞/巨噬细胞。出乎意料的是，我们在这里发现，KS是相当减少大鼠EAN。正常大鼠脊髓小胶质细胞仅表达KS。KS在前角小胶质细胞中阳性率为50%，在后角小胶质细胞中阳性率为20%。在EAN中，小胶质细胞的数量增加，并表达活化标志物CD 68，但KS表达被取消。同时，促炎细胞因子，即，EAN大鼠脊髓中IFN-γ、IL-1 β和TNF-α的表达增加，而抗炎细胞因子如IL-4和IL-10的表达减少。此外，在脂多糖和IFN-γ的刺激下，KSGal 6 ST的沉默减弱了原代培养小胶质细胞上KS的表达，并上调了一些激活标志物（TNF-α、IL-1β和iNOS）的表达。这项研究首次证明了EAN和KS在小胶质细胞上的消失的密切关联。KS表达可作为评价多发性神经病病情的一个有用指标。
Experimental autoimmune neuritis (EAN) is an animal model of Guillain–Barré syndrome, an inflammatory demyelination disease of the peripheral nervous system. Although this disease has been extensively studied on peripheral nerves, the pathology of the central nervous system has not been fully understood. Previous studies demonstrate that expression of keratan sulfate (KS), the sugar chain of proteoglycan, is associated with activated microglia/macrophages accumulated after neuronal injuries. Unexpectedly, we found here that KS is rather diminished in rat EAN. KS was restrictively expressed in microglia in the spinal cord of normal rats. KS was positive in 50% microglia in the ventral horn and 20% in the dorsal horn. In EAN, microglia increased in number and expressed the activation marker CD68, but KS expression was abolished. Concomitantly, pro-inflammatory cytokines, i.e., interferon (IFN)-γ, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α, were increased in the spinal cord of EAN rats, whereas anti-inflammatory cytokines, such as IL-4 and IL-10, were decreased. In addition, silencing of KSGal6ST attenuated KS expression on the primary cultured microglia and upregulated expression of some activation markers (TNF-α, IL-1β, and iNOS) under the stimulation with lipopolysaccharide and IFN-γ. This study demonstrates for the first time a close association of EAN and disappearance of KS on microglia. KS expression could be a useful marker to evaluate the status of polyneuropathy.
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DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG
影响因子：
9.3
作者：
Tauchi R;Imagama S;Natori T;Ohgomori T;Muramoto A;Shinjo R;Matsuyama Y;Ishiguro N;Kadomatsu K
通讯作者：
Kadomatsu K
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5.3
作者：
Jones, LL;Tuszynski, MH
通讯作者：
Tuszynski, MH
影响因子：
2.4
作者：
Hughes, RAC
通讯作者：
Hughes, RAC