title: Study of the anti-inflammatory effects of low-dose radiation: The contribution of biphasic regulation of the antioxidative system in endothelial cells.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiotherapy and Oncology, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany, franz.roedel@kgu.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Large
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hehlgans
authors.forename: Sebastian
authors.initials: S
authors.lastname: Reichert
authors.forename: Udo S
authors.initials: US
authors.lastname: Gaipl
authors.forename: Claudia
authors.initials: C
authors.lastname: Fournier
authors.forename: Claus
authors.initials: C
authors.lastname: Rödel
authors.forename: Christian
authors.initials: C
authors.lastname: Weiss
authors.forename: Franz
authors.initials: F
authors.lastname: Rödel
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000502:physiology* / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000532:radiotherapy*; D011829:Radiation Dosage; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species