Rödel Franz, Keilholz Ludwig, Herrmann Martin, Weiss Christian, Frey Benjamin, Voll Reinhard, Gaipl Udo, Rödel Claus
Department of Radiotherapy and Oncology, University Hospital of Frankfurt, Frankfurt, Germany.
Autoimmunity. 2009 May;42(4):343-5. doi: 10.1080/08916930902831597.
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.
低剂量放疗（LD-RT）已知具有抗炎作用。然而，其潜在的分子机制仍是当前研究的课题。我们最近发现，对受刺激的EA.hy.926内皮细胞（EC）进行低剂量放疗会导致核因子κB（NF-κB）呈现双相性的DNA结合和转录活性，同时白细胞黏附也呈双相过程。在此我们报告，通过电泳迁移率变动分析发现，低剂量X射线照射后，内皮细胞中活化蛋白1（AP-1）的DNA结合活性增加，在0.3 Gy时出现首个相对峰值。然后在0.5至1 Gy剂量之间AP-1活性下降，随后在3 Gy时再次升高。通过AP-1特异性化学发光报告基因检测在转录水平上证实了这种双相特征。总之，AP-1激活的不连续剂量反应可能为低剂量放疗抗炎功效的众多机制增添新的方面。
