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21 December 2016 Ionizing Radiation Induces Innate Immune Responses in Macrophages by Generation of Mitochondrial Reactive Oxygen Species
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Abstract

During radiotherapy for tumors, the innate immune system also responds to ionizing radiation and induces immune modulation. However, little is known about the molecular mechanisms by which radiation modulates innate immune responses. In this study, we observed that radiation triggered the generation of mitochondrial reactive oxygen species (mROS), leading to innate immune responses in murine bone marrow-derived macrophages (BMDM). Radiation-induced mROS was essential for robust induction of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-12p40 mRNA and protein in BMDM. Exposure to radiation also led to rapid activation of the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB pathways in BMDM. Notably, radiation-induced MAPK activation and NF-κB signaling were regulated by mROS in macrophages. Additionally, radiation-induced expression of TNF-α, IL-6 and IL-12p40 was dependent on JNK, p38 and NF-κB activation in BMDM. These data suggest a key role for radiation-induced pro-inflammatory responses and activation of the MAPK and NF-κB pathways through a triggering mechanism involving mROS generation.

©2017 by Radiation Research Society.
Sup Kim, Jin Ho Choe, Gippeum Joy Lee, Yi Sak Kim, Soo Yeon Kim, Hye-Mi Lee, Hyo Sun Jin, Tae Sung Kim, Jin-Man Kim, Moon-June Cho, Eui-Cheol Shin, Eun-Kyeong Jo, and Jun-Sang Kim "Ionizing Radiation Induces Innate Immune Responses in Macrophages by Generation of Mitochondrial Reactive Oxygen Species," Radiation Research 187(1), 32-41, (21 December 2016). https://doi.org/10.1667/RR14346.1
Received: 2 December 2015; Accepted: 1 September 2016; Published: 21 December 2016
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