TGFβ1 regulates the inflammatory response during chronic neurodegeneration
TGFβ1 regulates the inflammatory response during chronic neurodegeneration
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DOI：
10.1016/j.nbd.2006.01.004
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发表时间：
2006-06-01
影响因子：
6.1
通讯作者：
Perry, V. Hugh
中科院分区：
文献类型：
--
作者：
Boche, Delphine;Cunningham, Colm;Perry, V. Hugh
鼠朊病毒病的ME 7模型显示出非典型炎症反应，其特征是形态学活化的小胶质细胞和具有显着表达TGF β 1的抗炎细胞因子谱。对TGF β 1在时程疾病中的作用的研究表明，其表达与（i）行为异常的发作，（ii）活化的小胶质细胞增加，（iii）基底膜增厚，以及（iv）与PrPsc沉积增加相关。使用腺病毒载体增加TGF β 1对朊病毒相关的行为障碍或神经病理学没有显著影响。相反，使用表达核心蛋白聚糖的腺病毒抑制TGF β 1活性仅在朊病毒病动物中诱导严重的脑炎症、诱导型一氧化氮合酶的表达和急性神经元死亡。这些数据表明，TGF β 1在下调小胶质细胞反应中起关键作用，使脑炎症最小化，从而避免脑损伤的恶化。(c)2006年爱思唯尔公司All rights reserved.
The ME7 model of murine prion disease shows an atypical inflammatory response characterized by morphologically activated microglia and an anti-inflammatory cytokine profile with a marked expression of TGF beta 1. The investigation of the role of TGF beta 1 during a time course disease shows that its expression is correlated with (i) the onset of behavioral abnormalities, (ii) increased activated microglia, (iii) thickening of the basement membrane, and (iv) is associated with increased PrPsc deposition. Increasing TGF beta 1 using an adenoviral vector has no significant impact on prion-associated behavioral impairments or on neuropathology. In contrast, inhibition of TGF beta 1 activity using an adenovirus expressing decorin induces severe cerebral inflammation, expression of inducible nitric oxide synthase and acute neuronal death in prion-diseased animals only. These data suggest that TGF beta 1 plays a critical role in the downregulation of microglial responses minimizing brain inflammation and thus avoiding exacerbation of brain damage. (c) 2006 Elsevier Inc. All rights reserved.