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Ionizing radiation induces astrocyte gliosis through microglia activation.

Authors
Hwang, SY | Jung, JS | Kim, TH | Lim, SJ | Oh, ES | Kim, JY | Ji, KA | Joe, EH  | Cho, KH | Han, IO
Citation
Neurobiology of disease, 21(3). : 457-467, 2006
Journal Title
Neurobiology of disease
ISSN
0969-99611095-953X
Abstract
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)-1beta, 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-kappaB, a transcription factor that regulates microglial activation. Addition of prostaglandin E2 (PGE2: 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 PGE(2) 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.
MeSH

DOI
10.1016/j.nbd.2005.08.006
PMID
16202616
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Ajou Authors
조, 은혜
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