Ionizing radiation induces astrocyte gliosis through microglia activation.
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.
Hwang
So-Young
SY
Research Institute, National Cancer Center, Goyang, Gyeonggi, Korea.
Jung
Jae-Seob
JS
Kim
Tae-Hyun
TH
Lim
Soo-Jeong
SJ
Oh
Eok-Soo
ES
Kim
Joo-Young
JY
Ji
Kyung-Ae
KA
Joe
Eun-Hye
EH
Cho
Kwan-Ho
KH
Han
Inn-Oc
IO
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000528:radiation effects; D024202:Electrophoretic Mobility Shift Assay; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000209:etiology* / Q000473:pathology; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D009578:Nitrobenzenes / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011839:Radiation, Ionizing; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology
D017077:Culture Media, Conditioned; D016861:Cyclooxygenase Inhibitors; D005904:Glial Fibrillary Acidic Protein; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D015232:Dinoprostone