Delayed activation of human microglial cells by high dose ionizing radiation.
Recent studies have shown that microglia affects the fate of neural stem cells in response to ionizing radiation, which suggests a role for microglia in radiation-induced degenerative outcomes. We therefore investigated the effects of γ-irradiation on cell survival, proliferation, and activation of microglia and explored associated mechanisms. Specifically, we evaluated cellular and molecular changes associated with exposure of human microglial cells (CHME5) to low and high doses of acute cesium-137 γ rays. Twenty-four hours after irradiation, cell cycle analyses revealed dose-dependent decreases in the fraction of cells in S and G2/M phase, which correlated with significant oxidative stress. By one week after irradiation, 20-30% of the cells exposed to high doses of γ rays underwent apoptosis, which correlated with significant concomitant decrease in metabolic activity as assessed by the MTT assay, and microglial activation as judged by both morphological changes and increased expression of Glut-5 and CR43. These changes were associated with increases in the mRNA levels for IL-1α, IL-10 and TNFα. Together, the results show that human CHME5 microglia are relatively resistant to low and moderate doses of γ rays, but are sensitive to acute high doses, and that CHME5 cells are a useful tool for in vitro study of human microglia.
Department of Neurology and Neurosciences, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07103, United States.
Hongxin
H
Chen
Department of Neurology and Neurosciences, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07103, United States.
Zhao Zhong
ZZ
Chong
Department of Radiology, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07103, United States.
Sonia M
SM
De Toledo
Department of Radiology, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07103, United States.
Edouard I
EI
Azzam
Department of Neurology and Neurosciences, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07103, United States.
Stella
S
Elkabes
Department of Neurology and Neurosciences, New Jersey Medical School, Rutgers, the State University of New Jersey, Newark, NJ 07103, United States. Electronic address: souayani@njms.rutgers.edu.
Nizar
N
Souayah
D017209:Apoptosis / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D017628:Microglia / Q000378:metabolism / Q000528:radiation effects*; D018384:Oxidative Stress / Q000528:radiation effects
D016207:Cytokines
Brain; Cell death; Inflammation; Microglia; Radiation