title: The role of interleukin-13 in the removal of hyper-radiosensitivity by priming irradiation.
abstract: 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.
authors: Department of Physics, Biophysics Group, University of Oslo, PB 1048, Blindern, N-0316 Oslo, Norway n.f.j.edin@fys.uio.no.
authors: Nina F Jeppesen
authors: NF
authors: Edin
mesh_terms: D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D003470:Culture Media; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism*; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000378:metabolism; D018499:Linear Energy Transfer; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D043484:Proprotein Convertases / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011836:Radiation Tolerance / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D003470:Culture Media; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D010455:Peptides; D011498:Protein Precursors; D016212:Transforming Growth Factor beta; C472416:latency-associated propeptide, TGF-beta; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D043484:Proprotein Convertases
keywords: IL-13Rα2; iNOS; interleukin-13; low-dose hyper-radiosensitivity; proprotein convertase