Low-Dose Radiation Promotes Dendritic Cell Migration and IL-12 Production via the ATM/NF-KappaB Pathway
Low-Dose Radiation Promotes Dendritic Cell Migration and IL-12 Production via the ATM/NF-KappaB Pathway
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低剂量辐射通过 ATM/NF-KappaB 途径促进树突状细胞迁移和 IL-12 产生
DOI：
10.1667/rr14840.1
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发表时间：
2018
影响因子：
3.4
通讯作者：
Jiang Qisheng
中科院分区：
文献类型：
--
作者：
Yu Nan;Wang Sinian;Song Xiujun;Gao Ling;Li Wei;Yu Huijie;Zhou Chuanchuan;Zhenxia Wang;Fengsheng Li;Jiang Qisheng
对于树突状细胞（DC）启动免疫应答，其迁移和产生白细胞介素-12（IL-12）的能力至关重要。先前已经表明，低剂量辐射（LDR）促进DC产生IL-12，导致DC活性增加，这有助于免疫系统中的LDR兴奋效应。然而，LDR诱导IL-12产生的分子机制以及LDR对DC迁移能力的影响需要进一步阐明。使用JAWSII永生化小鼠树突状细胞系，我们表明，在体外X射线照射（0.2戈伊）的DC显着增加DC迁移和IL-12的生产，并上调CCR 7。针对CCR 7的中和抗体已显示消除LDR增强的DC迁移，表明CCR 7介导LDR促进DC迁移。我们将核因子κ B（NF-κB）确定为介导LDR增强的IL-12和CCR 7表达的中心信号通路，这是基于以下发现：0.2戈伊X射线照射激活NF-κB，显示核p65易位和NF-κB DNA结合活性增加，而NF-κB抑制剂阻断LDR增强的IL-12和CCR 7表达以及DC迁移。最后，我们证明了0.2戈伊X射线照射促进ATM磷酸化和活性氧的产生;然而，只有ATM抑制剂消除了LDR诱导的NF-κ B介导的IL-12和CCR 7表达。总之，我们的数据表明，暴露于LDR导致对DC的兴奋效应，通过激活ATM/NF-κB通路，使CCR 7介导的迁移和IL-12产生。
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.