Delayed activation of human microglial cells by high dose ionizing radiation

TY - JOUR

T1 - Delayed activation of human microglial cells by high dose ionizing radiation

AU - Chen, Hongxin

AU - Chong, Zhao Zhong

AU - De Toledo, Sonia M.

AU - Azzam, Edouard I.

AU - Elkabes, Stella

AU - Souayah, Nizar

N1 - Publisher Copyright: © 2016 Elsevier B.V.

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

KW - Brain

KW - Cell death

KW - Inflammation

KW - Microglia

KW - Radiation

UR - http://www.scopus.com/inward/record.url?scp=84973922609&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84973922609&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2016.06.002

DO - 10.1016/j.brainres.2016.06.002

M3 - Article

C2 - 27265419

SN - 0006-8993

VL - 1646

SP - 193

EP - 198

JO - Brain research

JF - Brain research

ER -