Ionizing Radiation Induces Innate Immune Responses in Macrophages by Generation of Mitochondrial Reactive Oxygen Species
| Autor: | Gippeum Joy Lee, Tae Sung Kim, Yi Sak Kim, Jin-Man Kim, Soo Yeon Kim, Jun-Sang Kim, Jin Ho Choe, Hye-Mi Lee, Eui-Cheol Shin, Moon-June Cho, Sup Kim, Eun-Kyeong Jo, Hyo Sun Jin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway MAP Kinase Signaling System p38 mitogen-activated protein kinases Interleukin-1beta Biophysics Bone Marrow Cells Biology p38 Mitogen-Activated Protein Kinases 03 medical and health sciences Mice Animals Radiology Nuclear Medicine and imaging RNA Messenger Protein kinase A chemistry.chemical_classification Reactive oxygen species Radiation Innate immune system Tumor Necrosis Factor-alpha Macrophages JNK Mitogen-Activated Protein Kinases NF-kappa B NFKB1 Cell biology Mitochondria Enzyme Activation Mice Inbred C57BL 030104 developmental biology chemistry Gene Expression Regulation Tumor necrosis factor alpha Female Signal transduction Signal Transduction |
| Zdroj: | Radiation research. 187(1) |
| ISSN: | 1938-5404 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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