Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain.
Irradiation induces regionally specific alterations in pro-inflammatory environments in rat brain.
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辐照引起大鼠脑促炎环境的区域特异性改变。
DOI：
10.3109/09553000903419346
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发表时间：
2010-02
影响因子：
2.6
通讯作者：
Lee, Yong Woo
中科院分区：
文献类型：
--
作者：
Lee, Won Hee;Sonntag, William E.;Mitschelen, Matthew;Yan, Han;Lee, Yong Woo
大脑中的促炎环境与神经系统疾病的发作和进展有关。在本研究中，我们调查的假设，脑照射诱导细胞因子基因和蛋白质表达的区域特异性改变。4月龄F344 × BN大鼠接受单次10戈伊γ射线全脑照射或假照射，照射后分别维持4、8和24 h。通过实时逆转录-聚合酶链反应（RT-PCR）、酶联免疫吸附试验（ELISA）和免疫荧光染色分析促炎介质的mRNA和蛋白表达水平。为了阐明辐射诱导的脑炎症的分子机制，还检测了辐射对促炎转录因子的DNA结合活性的影响。在海马和皮质区，观察到从辐射脑中分离的促炎介质，包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1β）和单核细胞趋化蛋白-1（MCP-1）的mRNA和蛋白表达显著上调。细胞因子表达具有区域特异性，因为与海马相比，皮质中TNF-α水平显著升高（高57%），与皮质样本相比，海马中IL-1β水平升高（高126%）。照射小鼠BV-2小胶质细胞后也观察到细胞因子水平增加。一系列电泳迁移率变动分析（EMSA）表明，辐射显著增加激活蛋白-1（AP-1）、核因子-κB（NF-κB）和cAMP反应元件结合蛋白（CREB）的活化。目前的研究表明，全脑照射通过激活AP-1、NF-κB和CREB以及TNF-α、IL-1β和MCP-1在大鼠脑中的过表达诱导区域特异性促炎环境，并且可能有助于辐射诱导的组织功能损伤的独特途径。
Pro-inflammatory environments in the brain have been implicated in the onset and progression of neurological disorders. In the present study, we investigate the hypothesis that brain irradiation induces regionally specific alterations in cytokine gene and protein expression. Four month old F344 × BN rats received either whole brain irradiation with a single dose of 10 Gy γ-rays or sham-irradiation, and were maintained for 4, 8, and 24 h following irradiation. The mRNA and protein expression levels of pro-inflammatory mediators were analysed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence staining. To elucidate the molecular mechanisms of irradiation-induced brain inflammation, effects of irradiation on the DNA-binding activity of pro-inflammatory transcription factors were also examined. A significant and marked up-regulation of mRNA and protein expression of pro-inflammatory mediators, including tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1), was observed in hippocampal and cortical regions isolated from irradiated brain. Cytokine expression was regionally specific since TNF-α levels were significantly elevated in cortex compared to hippocampus (57% greater) and IL-1β levels were elevated in hippocampus compared to cortical samples (126% greater). Increases in cytokine levels also were observed after irradiation of mouse BV-2 microglial cells. A series of electrophoretic mobility shift assays (EMSA) demonstrated that irradiation significantly increased activation of activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and cAMP response element-binding protein (CREB). The present study demonstrated that whole brain irradiation induces regionally specific pro-inflammatory environments through activation of AP-1, NF-κB, and CREB and overexpression of TNF-α, IL-1β, and MCP-1 in rat brain and may contribute to unique pathways for the radiation-induced impairments in tissue function.
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影响因子：
3.3
作者：
BLASI, E;BARLUZZI, R;BISTONI, F
通讯作者：
BISTONI, F
影响因子：
3.1
作者：
Deng, XQ;Li, HJ;Tang, YW
通讯作者：
Tang, YW
DOI：
10.1016/s0169-328x(97)00190-3
发表时间：
1997-10-15
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Iwata, E;Asanuma, M;Ogawa, N
通讯作者：
Ogawa, N
影响因子：
3.4
作者：
Johnston, CJ;Williams, JP;Finkelstein, JN
通讯作者：
Finkelstein, JN
DOI：
10.1016/s0169-328x(02)00353-4
发表时间：
2002-08-15
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Kyrkanides, S;Moore, AH;O'Banion, MK
通讯作者：
O'Banion, MK