Activator protein 1 shows a biphasic induction and transcriptional activity after low dose X-irradiation in EA.hy.926 endothelial cells.
Low dose radiotherapy (LD-RT) is known to exert an anti-inflammatory effect. The underlying molecular mechanisms, however, are still a matter of actual research. We have recently shown that LD-RT of stimulated EA.hy.926 endothelial cells (EC) resulted in a biphasic DNA-binding and transcriptional activity of NF-kappaB in parallel with a biphasic course of leukocyte adhesion. Here we report, that following low dose X-irradiation, an increased activator protein 1 (AP-1) DNA-binding activity was observed in EC with a first relative maximum at 0.3 Gy as analysed by electrophoretic mobility shift assay. AP-1 activity then decreased at doses between 0.5 and 1 Gy and subsequently increased again at 3 Gy. This biphasic profile was confirmed on the transcriptional level by an AP-1 specific chemoluminescence reporter assay. In conclusion, the discontinuous dose response of AP-1 activation may add a further facet to the plethora of mechanisms contributing to the anti-inflammatory efficacy of LD-RT.
Rödel
Franz
F
Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Frankfurt, Germany. franz.roedel@kgu.de
Keilholz
Ludwig
L
Herrmann
Martin
M
Weiss
Christian
C
Frey
Benjamin
B
Voll
Reinhard
R
Gaipl
Udo
U
Rödel
Claus
C
D004307:Dose-Response Relationship, Radiation; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000378:metabolism / Q000528:radiation effects*; D015870:Gene Expression / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*
D018808:Transcription Factor AP-1