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8 February 2018 Low-Dose Radiation Promotes Dendritic Cell Migration and IL-12 Production via the ATM/NF-KappaB Pathway
Nan Yu, Sinian Wang, Xiujun Song, Ling Gao, Wei Li, Huijie Yu, Chuanchuan Zhou, Zhenxia Wang, Fengsheng Li, Qisheng Jiang
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Abstract

For dendritic cells (DCs) to initiate an immune response, their ability to migrate and to produce interleukin-12 (IL-12) is crucial. It has been previously shown that low-dose radiation (LDR) promoted IL-12 production by DCs, resulting in increased DC activity that contributed to LDR hormesis in the immune system. However, the molecular mechanism of LDR-induced IL-12 production, as well as the effect of LDR on DC migration capacity require further elucidation. Using the JAWSII immortalized mouse dendritic cell line, we showed that in vitro X-ray irradiation (0.2 Gy) of DCs significantly increased DC migration and IL-12 production, and upregulated CCR7. The neutralizing antibody against CCR7 has been shown to abolish LDR-enhanced DC migration, demonstrating that CCR7 mediates LDR-promoting DC migration. We identified nuclear factor kappaB (NF-κB) as the central signaling pathway that mediated LDR-enhanced expression of IL-12 and CCR7 based on findings that 0.2 Gy X-ray irradiation activated NF-κB, showing increased nuclear p65 translocation and NF-κB DNA-binding activity, while an NF-κB inhibitor blocked LDR-enhanced expression of IL-12 and CCR7, as well as DC migration. Finally, we demonstrated that 0.2 Gy X-ray irradiation promoted ATM phosphorylation and reactive oxygen species generation; however, only the ATM inhibitor abolished the LDR-induced NF-κB-mediated expression of IL-12 and CCR7. Altogether, our data show that exposure to LDR resulted in a hormetic effect on DCs regarding CCR7-mediated migration and IL-12 production by activating the ATM/NF-κB pathway.

©2018 by Radiation Research Society.
Nan Yu, Sinian Wang, Xiujun Song, Ling Gao, Wei Li, Huijie Yu, Chuanchuan Zhou, Zhenxia Wang, Fengsheng Li, and Qisheng Jiang "Low-Dose Radiation Promotes Dendritic Cell Migration and IL-12 Production via the ATM/NF-KappaB Pathway," Radiation Research 189(4), 409-417, (8 February 2018). https://doi.org/10.1667/RR14840.1
Received: 23 May 2017; Accepted: 1 January 2018; Published: 8 February 2018
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