Ionizing Radiation Induces Innate Immune Responses in Macrophages by Generation of Mitochondrial Reactive Oxygen Species
Ionizing Radiation Induces Innate Immune Responses in Macrophages by Generation of Mitochondrial Reactive Oxygen Species
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DOI：
10.1667/rr14346.1
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发表时间：
2017-01-01
影响因子：
3.4
通讯作者：
Kim, Jun-Sang
中科院分区：
文献类型：
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作者：
Kim, Sup;Choe, Jin Ho;Kim, Jun-Sang
在肿瘤的放射治疗期间，先天免疫系统也对电离辐射作出反应并诱导免疫调节。然而，人们对辐射调节先天免疫反应的分子机制知之甚少。在这项研究中，我们观察到，辐射触发线粒体活性氧（mROS）的产生，导致小鼠骨髓源性巨噬细胞（BMDM）的先天免疫反应。辐射诱导的mROS对于BMDM中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和IL-12 p40 mRNA和蛋白的稳健诱导是必不可少的。辐射暴露也导致BMDM中丝裂原活化蛋白激酶（MAPK）和核因子（NF）-κ B途径的快速激活。值得注意的是，辐射诱导的MAPK激活和NF-κ B信号传导受到巨噬细胞中mROS的调节。此外，辐射诱导的TNF-α、IL-6和IL-12 p40表达依赖于JNK、p38和NF-κ B激活。这些数据表明，辐射诱导的促炎反应和活化的MAPK和NF-κ B途径通过触发机制涉及mROS的产生的关键作用。(C)2017辐射研究学会
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-alpha (TNF-alpha), 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)-kappa B pathways in BMDM. Notably, radiation-induced MAPK activation and NF-kappa B signaling were regulated by mROS in macrophages. Additionally, radiation-induced expression of TNF-alpha, IL-6 and IL-12p40 was dependent on JNK, p38 and NF-kappa B activation in BMDM. These data suggest a key role for radiation-induced pro-inflammatory responses and activation of the MAPK and NF-kappa B pathways through a triggering mechanism involving mROS generation. (C) 2017 by Radiation Research Society