Ionizing radiation induces astrocyte gliosis through microglia activation

So Young Hwang, Jae Seob Jung, Tae Hyun Kim, Soo Jeong Lim, Eok Soo Oh, Joo Young Kim, Kyung Ae Ji, Eun Hye Joe, Kwan Ho Cho, Inn Oc Han

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

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)-1β, IL-6, IL-18, tumor necrosis factor-α and interferon-γ-inducible protein-10, which are usually associated with microglia activation. Consistent with these findings, irradiation of microglia activated NF-κB, 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 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.

Original languageEnglish
Pages (from-to)457-467
Number of pages11
JournalNeurobiology of Disease
Volume21
Issue number3
DOIs
StatePublished - Mar 2006

Keywords

  • Astrocyte
  • COX-2
  • Microglia
  • Radiation

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