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01.09.2015 | Original Article

Study of the anti-inflammatory effects of low-dose radiation

The contribution of biphasic regulation of the antioxidative system in endothelial cells

verfasst von: Martin Large, MSc, Stephanie Hehlgans, PhD, Sebastian Reichert, PhD, Udo S. Gaipl, PhD, Claudia Fournier, PhD, Claus Rödel, MD, Christian Weiss, MD, Prof. Dr. rer. nat. Franz Rödel, PhD

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 9/2015

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Abstract

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.

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Titel: Study of the anti-inflammatory effects of low-dose radiation
The contribution of biphasic regulation of the antioxidative system in endothelial cells
verfasst von: Martin Large, MSc
Stephanie Hehlgans, PhD
Sebastian Reichert, PhD
Udo S. Gaipl, PhD
Claudia Fournier, PhD
Claus Rödel, MD
Christian Weiss, MD
Prof. Dr. rer. nat. Franz Rödel, PhD
Publikationsdatum: 01.09.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Strahlentherapie und Onkologie / Ausgabe 9/2015
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI: https://doi.org/10.1007/s00066-015-0848-9

Neu im Fachgebiet Onkologie

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Study of the anti-inflammatory effects of low-dose radiation

The contribution of biphasic regulation of the antioxidative system in endothelial cells

Abstract

Background

Material and methods

Results

Conclusion

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