Effect of Cobalt-60 Irradiation on Bradykinin B2 Receptor Expression on Human HF-15 Cells

Abstract

Bradykinin is a key mediator of pain and inflammation. Although radiotherapy has proven to be beneficial in the treatment of inflammatory disorders, the effect of irradiation on the bradykinin pathway in human cells has not been evaluated yet. Therefore, the aim of the study was to establish a human cell culture system and to analyze bradykinin B2 receptor expression in response to different doses of gamma-ray exposure. Cultured human foreskin fibroblasts (HF15) were irradiated with 0.5 Gy, 2.0 Gy, 5.0 Gy and 10.0 Gy single doses using a Cobalt 60 radiation source. Before treatment (0h) as well as 6, 24, and 48 hours after radiation the bradykinin receptor surface density was quantified by a ligand binding assay using radioactive [3H]bradykinin. A dose and time dependant expression of the bradykinin B2 receptor was observed. Initially, higher doses (2 and 10 Gy) induced a fast upregulation of the receptor, followed by long lasting downregulation compared to baseline levels. In contrast the lowest dose (0.5 Gy) induced a fast down regulation of the receptor. After 24 h and 48 h the levels increased again but remained below baseline levels. A dose- and time-dependant change in bradykinin B2 receptor expression on HF-15-cells in response to irradiation was demonstrated. The results may imply radio-biological explanations for the beneficial effect of radiotherapy in benign inflammatory diseases.