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Low-Dose Radiation Promotes Dendritic Cell Migration and IL-12 Production via the ATM/NF-KappaB Pathway.
- Source :
-
Radiation research [Radiat Res] 2018 Apr; Vol. 189 (4), pp. 409-417. Date of Electronic Publication: 2018 Feb 08. - Publication Year :
- 2018
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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.
- Subjects :
- Animals
Cell Line
Dendritic Cells cytology
Dendritic Cells metabolism
Dose-Response Relationship, Radiation
Mice
Receptors, CCR7 metabolism
Ataxia Telangiectasia Mutated Proteins metabolism
Cell Movement radiation effects
Dendritic Cells radiation effects
Interleukin-12 biosynthesis
NF-kappa B metabolism
Signal Transduction radiation effects
Subjects
Details
- Language :
- English
- ISSN :
- 1938-5404
- Volume :
- 189
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Radiation research
- Publication Type :
- Academic Journal
- Accession number :
- 29420126
- Full Text :
- https://doi.org/10.1667/RR14840.1