The role of interleukin-13 in the removal of hyper-radiosensitivity by priming irradiation

It has previously been demonstrated that the presence of fetal bovine serum is necessary for tgf-β3 (transforming growth factor beta 3)-dependent elimination of low-dose hyper-radiosensitivity (hrs) in cells by 1 h of low-dose-rate γ-irradiation (0.2-0.3 gy/h). the purpose of the present study was to identify the serum constituent involved. two human hrs-positive (t-47d,t98g) cell lines were used. the effects of different pretreatments on hrs were investigated using the colony assay. total inducible nitric oxide synthase (inos) levels were measured using a cell-based elisa assay. the serum factor was identified as interleukin-13 (il-13). in order for low dose-rate irradiation to eliminate hrs through the tgf-β3-dependent mechanism,the cells must be exposed to il-13 first. inhibiting receptor il-13rα2 showed that this receptor is involved in the response. adding il-13 to serum-free medium restored the properties of full medium but not when an inhibitor of proprotein convertase activity was added together with il-13. the presence of il-13 resulted in upregulation of total inos protein levels. thus,this study indicates that il-13 interacts with the cells though receptor il-13rα2 and induces upregulation of inos and activation of one or more furin-like proprotein convertases. © the author 2014. published by oxford university press on behalf of the japan radiation research society and japanese society for radiation oncology.