Regulation of microglial activities by glial cell line derived neurotrophic factor
Regulation of microglial activities by glial cell line derived neurotrophic factor
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DOI：
10.1002/jcb.20646
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发表时间：
2006-02-15
影响因子：
4
通讯作者：
Tzeng, SF
中科院分区：
文献类型：
--
作者：
Chang, YP;Fang, KM;Tzeng, SF
胶质细胞源性神经营养因子（GDNF）对中枢神经系统神经元的保护作用已引起广泛关注。然而，GDNF对也能表达GDNF受体系统的CNS胶质细胞的作用知之甚少。在这项研究中，我们研究了GDNF对原代大鼠小胶质细胞的影响，这些小胶质细胞在CNS中起着常驻巨噬细胞的作用，并在激活时作为促炎介质的来源。我们发现用GDNF处理原代大鼠小胶质细胞对促炎细胞因子肿瘤坏死因子-α（TNF-α）和白细胞介素-1 β（IL-1 β）的分泌没有影响，但在一定程度上增加了一氧化氮（NO）的产生。此外，GDNF增加了超氧化物歧化酶（SOD）的酶活性，表面抗原细胞间粘附分子-1（ICAM-1）的基因表达，整合素α 5亚基的产生，以及原代大鼠小胶质细胞的吞噬能力。U 0126对小鼠小胶质细胞系BV 2中丝裂原活化蛋白激酶（mitogen-activated protein kinase，Erk-MAPK）的抑制作用表明，GDNF可能通过MAP激酶信号通路调节NO和整合素α 5的产生。体内实验也显示，脊髓损伤后1周，GDNF处理的脊髓组织中出现了整合素α 5或ED 1免疫反应性的阿米巴样细胞。U 0126对小鼠小胶质细胞BV 2中Erk-MAPK的抑制作用表明，GDNF可能通过MAP激酶信号通路调节NO和整合素α 5的产生。总之，我们的结果表明，GDNF对小胶质细胞的活动具有积极的调节作用，如吞噬作用和粘附分子的上调。
Much attention has been paid to the ability of glial cell-line-derived neurotrophic factor (GDNF) to protect neurons from neurotoxic insults in the central nervous system (CNS). However, little is known a bout GDNF action on CNS glia that also can express GDNF receptor systems. In this study, we examined the effects of GDNF on primary rat microglia that function as resident macrophages in the CNS and as the Source of proinflammatory mediators upon activation. We found that treatment of primary rat microglia with GDNF had no effect on the secretion of the proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), but it increased the nitric oxide (NO) production to some extent. In addition, GDNF increased the enzymatic activity of Superoxide dismutase (SOD), the gene expression of surface antigen intercellular adhesion molecule-1 (ICAM-1), the production of the integrin alpha 5 Subunit, and the phagocytotic capability in primary rat microglia. Furthermore, inhibition of mitogen-activated protein kinase (Erk-MAPK) in the mouse microglial cell line BV2 by U0126 indicated that the MAP kinase signaling pathway may be involved in the regulation of NO and integrin a5 production by GDNF. In vivo evidence also showed that amoeboid cells with integrin alpha 5 or with ED1 immunoreactivity appeared in GDNF-treated spinal cord tissues at the lesion site 1 week post spinal cord injury (SCI). Furthermore, inhibition of Erk-MAPK in the mouse microglial cell line BV2 by U0126 indicated that the MAP kinase signaling pathway may be involved in the regulation of NO and integrin a5 production by GDNF. Taken together, Our results indicate that GDNF has a positive regulatory effect on microglial activities, Such as phagocytosis and the upregulation of adhesion molecules.