High interleukin-10 expression within the central nervous system may be important for initiation of recovery of Dark Agouti rats from experimental autoimmune encephalomyelitis
High interleukin-10 expression within the central nervous system may be important for initiation of recovery of Dark Agouti rats from experimental autoimmune encephalomyelitis
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DOI：
10.1016/j.imbio.2013.04.004
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发表时间：
2013-09-01
期刊：
影响因子：
2.8
通讯作者：
Stojkovic, Marija Mostarica
中科院分区：
文献类型：
--
作者：
Blazevski, Jana;Petkovic, Filip;Stojkovic, Marija Mostarica
Dark Agti(DA)大鼠对实验性自身免疫性脑脊髓炎(EAE)的诱导非常敏感，但仍能完全康复。在此，我们有兴趣确定主要的抗炎细胞因子转化生长因子(TGF)-β和白介素10(IL-10)在DA大鼠从EAE中恢复的作用。为此，我们测定了DA大鼠在EAE不同阶段的中枢神经系统中这些细胞因子的表达，并与EAE抵抗的牛津白化(AO)大鼠的数据进行了比较。即使未免疫大鼠，也可观察到转化生长因子-β在AO大鼠中枢神经系统中持续高表达。提示中枢神经系统内高水平的转化生长因子-β在AO大鼠抵抗EAE诱导中起重要作用。相反，DA大鼠IL-10的表达一直高于AO大鼠，并在EAE高峰期达到高峰。甲基强的松龙可抑制脊髓匀浆中EAE和IL-10的表达，而增加中枢神经系统浸润性免疫细胞中IL-10的表达。提示IL-10在DA大鼠的康复过程中可能起重要作用。因此，我们接下来探索了IL-10对星形胶质细胞的影响，星形胶质细胞在很大程度上有助于控制中枢神经系统的炎症。IL-10刺激神经炎症重要调节因子CXCL12的星形胶质细胞表达。因此，IL-10可能通过诱导星形胶质细胞表达CXCL12而促进DA大鼠从EAE中恢复。(C)2013年爱思唯尔股份有限公司。版权所有。
Dark Agouti (DA) rats are highly susceptible to induction of experimental autoimmune encephalomyelitis (EAE), still they completely recover from the disease. Here, we were interested to determine contribution of major anti-inflammatory cytokines transforming growth factor (TGF)-beta and interleukin (IL)-10 to the recovery of DA rats from EAE. To that extent we determined CNS expression of these cytokines in DA rats at different phases of EAE and compared data to those obtained in EAE-resistant Albino Oxford (AO) rats. Higher expression of TGF-beta was persistently observed in the CNS of AO rats, even if rats were not immunized. This implied that high TGF-beta within the CNS is important for resistance of AO rats to EAE induction. On the contrary, IL-10 expression was consistently higher in DA than in AO rats and it culminated at the peak of EAE. Methylprednisolone suppressed EAE and expression of IL-10 in spinal cord homogenates, while IL-10 was increased in CNS-infiltrating immune cells. This implied that IL-10 might have a significant role in recovery of DA rats from the disease. Thus, we next explored effects of IL-10 on astrocytes, glial cells that largely contribute to control of CNS inflammation. IL-10 stimulated astrocytic expression of an important regulator of neuroinflammation, CXCL12. Thus, IL-10 might contribute to recovery of DA rats from EAE through induction of CXCL12 expression in astrocytes. (C) 2013 Elsevier GmbH. All rights reserved.