Ionizing radiation induces astrocyte gliosis through microglia activation
Ionizing radiation induces astrocyte gliosis through microglia activation
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DOI：
10.1016/j.nbd.2005.08.006
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发表时间：
2006-03-01
影响因子：
6.1
通讯作者：
Han, IO
中科院分区：
文献类型：
--
作者：
Hwang, SY;Jung, JS;Han, IO
本研究旨在探讨小胶质细胞在辐射诱导的星形胶质细胞形成中的作用。我们发现，单剂量的15 Gy全脑辐射在6小时后增加了星形胶质细胞中胶质原纤维酸性蛋白的免疫染色，24小时后甚至更多，表明胶质细胞形成的开始。虽然对培养的大鼠星形胶质细胞的照射作用不大，但对小胶质细胞-星形胶质细胞混合培养的照射显示星形胶质细胞表型改变，变得更加工，这是胶质瘤的另一个特征。使用小胶质细胞条件培养基的实验表明，这种星形胶质细胞的变化是由于受辐照的小胶质细胞释放的因素。辐照培养的小鼠小胶质细胞诱导环氧化酶-2 （COX-2）、白细胞介素(IL)-1 β、IL-6、IL-18、肿瘤坏死因子α和干扰素- γ诱导蛋白-10 mRNA水平呈剂量依赖性增加，这些mRNA水平通常与小胶质细胞活化有关。与这些发现一致，照射小胶质细胞激活了NF-kappa B，一种调节小胶质细胞激活的转录因子。将前列腺素E-2 （PGE(2): COX-2酶的代谢产物）添加到原代培养的大鼠星形胶质细胞中，导致与混合培养实验相似的表型变化。因此，从辐照小胶质细胞释放的PGE2似乎是辐照诱导的胶质细胞形成或星形胶质细胞表型改变的关键介质。这些数据表明，放射诱导的小胶质细胞活化和由此产生的PGE2似乎与恶性胶质瘤放射治疗相关的炎症并发症的潜在原因有关。(C) 2005爱思唯尔公司版权所有。
The aim of this study was to investigate the role of microglia in radiation-induced astrocyte gliosis. We found that a single dose of 15 Gy radiation to a whole rat brain increased immunostaining of glial fibrillary acidic protein in astrocytes 6 h later, and even more so 24 h later, indicating the initiation of gliosis. While irradiation of cultured rat astrocytes had little effect, irradiation of microglia-astrocyte mixed-cultures displayed altered astrocyte phenotype into more processed, which is another characteristic of gliosis. Experiments using microglia-conditioned media indicated this astrocyte change was due to factors released from irradiated microglia. Irradiation of cultured mouse microglial cells induced a dose-dependent increase in mRNA levels for cyclooxygenase-2 (COX-2), interleukin (IL)-1 beta, IL-6, IL-18, tumor necrosis factor-alpha and interferon-gamma-inducible protein-10, which are usually associated with microglia activation. Consistent with these findings, irradiation of microglia activated NF-kappa B, a transcription factor that regulates microglial activation. Addition of prostaglandin E-2 (PGE(2): a metabolic product of the COX-2 enzyme) to primary cultured rat astrocytes resulted in phenotypic changes similar to those observed in mixed-culture experiments. Therefore, it appears that PGE2 released from irradiated microglia is a key mediator of irradiation-induced gliosis or astrocyte phenotype change. These data suggest that radiation-induced microglial activation and resultant production of PGE2 seems to be associated with an underlying cause of inflammatory complications associated with radiation therapy for malignant gliomas. (C) 2005 Elsevier Inc. All rights reserved.