Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury.
Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury.
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DOI：
10.1084/jem.20041918
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发表时间：
2005-07-04
影响因子：
15.3
通讯作者：
Bethea, JR
中科院分区：
文献类型：
--
作者：
Brambilla, R;Bracchi-Ricard, V;Hu, WH;Frydel, B;Bramwell, A;Karmally, S;Green, EJ;Bethea, JR
在中枢神经系统（CNS）中，转录因子核因子（NF）-κB是炎症和继发性损伤过程的关键调节因子。在创伤或疾病后，NF-κ B依赖性基因的表达被高度激活，导致对CNS恢复的保护和有害作用。我们证明，选择性灭活星形胶质细胞NF-κB在转基因小鼠（胶质细胞酸性蛋白[GFAP]-dn小鼠）中表达的显性负性（dn）形式的抑制剂κBα在星形胶质细胞特异性启动子的控制下，导致功能恢复显着改善后8周挫伤性脊髓损伤（SCI）。在组织学上，GFAP小鼠表现出减少的病变体积和显著增加的白色物质保留。同时，它们显示促炎趋化因子和细胞因子（如CXCL 10、CCL 2和转化生长因子-β2）以及参与神经胶质瘢痕形成的硫酸软骨素蛋白聚糖的表达减少。我们的结论是选择性抑制星形胶质细胞中的NF-κB信号导致SCI后的保护作用，并提出NF-κB通路作为开发SCI治疗策略的可能新靶点。
In the central nervous system (CNS), the transcription factor nuclear factor (NF)-κB is a key regulator of inflammation and secondary injury processes. After trauma or disease, the expression of NF-κB–dependent genes is highly activated, leading to both protective and detrimental effects on CNS recovery. We demonstrate that selective inactivation of astroglial NF-κB in transgenic mice expressing a dominant negative (dn) form of the inhibitor of κBα under the control of an astrocyte-specific promoter (glial fibrillary acidic protein [GFAP]–dn mice) leads to a dramatic improvement in functional recovery 8 wk after contusive spinal cord injury (SCI). Histologically, GFAP mice exhibit reduced lesion volume and substantially increased white matter preservation. In parallel, they show reduced expression of proinflammatory chemokines and cytokines, such as CXCL10, CCL2, and transforming growth factor–β2, and of chondroitin sulfate proteoglycans participating in the formation of the glial scar. We conclude that selective inhibition of NF-κB signaling in astrocytes results in protective effects after SCI and propose the NF-κB pathway as a possible new target for the development of therapeutic strategies for the treatment of SCI.
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影响因子：
8.3
作者：
Acarin, L;González, B;Castellano, B
通讯作者：
Castellano, B
影响因子：
4.8
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Beni, SM;Kohen, R;Shohami, E
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Shohami, E
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Bolego, C;Ceruti, S;Abbracchio, MP
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Abbracchio, MP
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作者：
Davies, JE;Tang, XF;Davies, SJA
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Davies, SJA
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64.8
作者：
BEG, AA;SHA, WC;BALTIMORE, D
通讯作者：
BALTIMORE, D