The induction of TGF-beta(1) and NF-kappaB parallels a biphasic time course of leukocyte/endothelial cell adhesion following low-dose X-irradiation.

摘要: Low-dose radiotherapy (LD-RT) is known to exert an anti-inflammatory effect, but the knowledge of underlying molecular mechanisms still scarce. The authors have recently reported that transforming growth factor beta 1 (TGF-β1) essentially contributes a reduced endothelial adhesion mononuclear cells (PBMC) following LD-RT. Furthermore, TGF-β1 secretion was associated with induction transcription factor nuclear kappa B (NF-κB). However, time course of adhesion, TGF-β1 expression, and NF-κB activity following LD-RT has not been thoroughly investigated yet. human EA.hy.926 cell line (EA.hy.926 EC) was grown 95% confluence. Immediately after stimulation with the pro-inflammatory cytokine tumor necrosis alpha (TNF-α), EC were irradiated single doses ranging from 0.3 up 3 Gy. Adhesion assays performed 4, 12, and 24 h irradiation. Nuclear extracts culture supernatants harvested 8, 20, 24, 30, 40 h. NF-κB DNA-binding activity analyzed by electrophoretic mobility shift (EMSA) enzyme-linked immunosorbent assay (ELISA). The functional impact on leukocyte/EC neutralizing TGF-β1 in parallel with stimulation/irradiation EC. 4 24 irradiation dose range between 0.7 Gy, a reduced PBMC compared nontreated controls could be observed. 12 h after relative maximum (up 30% increase) seen at dose Gy. TGF-β1 secretion DNA-binding activity displayed similar biphasic kinetics with a minimum Neutralization of TGF-β1 restored 4 and EC, it did influence leukocyte stimulated followed a biphasic course an increased secretion TGF-β1. shows peak levels 4–8 24–30 results profile.