Neuromelanin inhibits CXCL10 expression in human astroglial cells.
Neuromelanin inhibits CXCL10 expression in human astroglial cells.
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DOI：
10.1016/j.neulet.2010.09.042
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发表时间：
2010-12-03
影响因子：
2.5
通讯作者：
Davis RL
中科院分区：
文献类型：
--
作者：
Tousi NS;Buck DJ;Zecca L;Davis RL
越来越多的证据表明，神经炎症在帕金森病(PD)的发病机制中起着重要作用。在帕金森病患者中，含有神经黑素(NM)的多巴胺神经元发生选择性变性。神经黑素在多巴胺能神经元中主要是细胞保护作用，而受损神经元释放的NM则激活小胶质细胞。然而，NM对星形胶质细胞的影响在很大程度上仍不清楚。星形胶质细胞对神经元的动态平衡和损伤反应是必不可少的，部分是通过分泌趋化因子，包括干扰素γ诱导蛋白-10(CXCL10)。因此，我们使用体外实验的方法来确定NM对肿瘤坏死因子α诱导的人脑星形胶质细胞CXCL10表达的影响。在NM暴露的细胞中，肿瘤坏死因子α诱导的CXCL10表达受到抑制。此外，NM可抑制肿瘤坏死因子α诱导的NF-κB活化。鉴于CXCL10在人脑星形胶质细胞中的表达是依赖于NF-κB的，这些发现提示NM可能部分通过依赖于NF-κB的机制来抑制CXCL10的表达。虽然NM对星形胶质细胞CXCL10表达的体内影响仍未完全阐明，但本研究获得的见解进一步加深了我们对NM对人脑星形胶质细胞炎症信号的影响的理解。
Increasing evidence indicates neuroinflammation is instrumental in the pathogenesis of Parkinson's disease (PD). In PD, there is selective degeneration of neuromelanin (NM)-containing dopamine neurons. Neuromelanin is predominantly cytoprotective within dopaminergic neurons, whereas, NM released from damaged neurons activates microglia. However, the effects of NM on astroglial cells remain largely unknown. Astroglia are essential to neuronal homeostasis and responsive to injury, in part, through secretion of chemokines, including interferon γ inducible protein-10 (CXCL10). Thus, we used an in vitro approach to identify the effects of NM on TNFα-induced CXCL10 expression in human astroglial cells. TNFα-induced CXCL10 expression was inhibited in NM exposed cells. Additionally, TNFα-induced NF-κB activation was inhibited by NM. Given that CXCL10 expression is NF-κB-dependent in human astroglial cells, these findings suggest that NM may inhibit CXCL10 expression, in part, through an NF-κB-dependent mechanism. While the in vivo consequences of NM mediated effects on astroglial CXCL10 expression remain to be fully elucidated, insights obtained in this study further our understanding of the effects of NM on inflammatory signaling in human astroglial cells.
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影响因子：
15.3
作者：
Brambilla, R;Bracchi-Ricard, V;Hu, WH;Frydel, B;Bramwell, A;Karmally, S;Green, EJ;Bethea, JR
通讯作者：
Bethea, JR
影响因子：
3.3
作者：
Flynn, G;Maru, S;Male, D
通讯作者：
Male, D
影响因子：
12.7
作者：
Itoh, K;Mehraein, P;Weis, S
通讯作者：
Weis, S
DOI：
10.1523/jneurosci.4144-09.2009
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：
Ghosh A;Roy A;Matras J;Brahmachari S;Gendelman HE;Pahan K
通讯作者：
Pahan K
影响因子：
8.6
作者：
Banati, RB;Daniel, SE;Blunt, SB
通讯作者：
Blunt, SB