Study of the anti-inflammatory effects of low-dose radiation: The contribution of biphasic regulation of the antioxidative system in endothelial cells

Strahlenther Onkol. 2015 Sep;191(9):742-9. doi: 10.1007/s00066-015-0848-9. Epub 2015 Jun 8.


Background: We examined (a) the expression of the antioxidative factor glutathione peroxidase (GPx) and the transcription factor nuclear factor E2-related factor 2 (Nrf2) following low-dose X-irradiation in endothelial cells (ECs) and (b) the impact of reactive oxygen species (ROS) and Nrf2 on functional properties of ECs to gain further knowledge about the anti-inflammatory mode of action of low doses of ionizing radiation.

Material and methods: EA.hy926 ECs and primary human dermal microvascular ECs (HMVEC) were stimulated by tumor necrosis factor-α (TNF-α, 20 ng/ml) 4 h before irradiation with single doses ranging from 0.3 to 3 Gy. The expression and activity of GPx and Nrf2 were analyzed by flow cytometry, colorimetric assays, and real-time PCR. The impact of ROS and Nrf2 on peripheral blood mononuclear cell (PBMC) adhesion was assayed in the presence of the ROS scavenger N-acetyl-L-cysteine (NAC) and Nrf2 activator AI-1.

Results: Following a low-dose exposure, we observed in EA.hy926 EC and HMVECs a discontinuous expression and enzymatic activity of GPx concomitant with a lowered expression and DNA binding activity of Nrf2 that was most pronounced at a dose of 0.5 Gy. Scavenging of ROS by NAC and activation of Nrf2 by AI-1 significantly diminished a lowered adhesion of PBMC to EC at a dose of 0.5 Gy.

Conclusion: Low-dose irradiation resulted in a nonlinear expression and activity of major compounds of the antioxidative system that might contribute to anti-inflammatory effects in stimulated ECs.

MeSH terms

  • Antioxidants / metabolism*
  • Cell Adhesion / physiology
  • Cell Adhesion / radiation effects
  • Cells, Cultured
  • Dose-Response Relationship, Radiation
  • Endothelial Cells / physiology*
  • Endothelial Cells / radiation effects*
  • Gene Expression Regulation / physiology
  • Gene Expression Regulation / radiation effects
  • Humans
  • Inflammation / metabolism*
  • Inflammation / radiotherapy*
  • Radiation Dosage
  • Reactive Oxygen Species / metabolism*


  • Antioxidants
  • Reactive Oxygen Species