High-dose Radiation Induces an Early and Transient, ATM-dependent Inflammatory Response in Primary Human Endothelial Cells.

Inflammation is the initial immune response activated to protect an organism's integrity after cell or tissue damage caused by infectious agents or physical trauma, such as exposure to ionizing radiation. The mechanisms behind ionizing radiation-induced inflammation are not fully understood in untransformed human cells, especially at high dose exposures that can also cause cell death. Radiation-induced genotoxic stress triggers the cellular DNA damage response, and interactions between this pathway and inflammation may be crucial in determining the fate of irradiated cells. We studied how primary human vascular endothelial cells, telomerase-immortalized foreskin microvascular cells, blood mononuclear cells, and primary skin fibroblasts respond to radiation doses from 2 to 10 Gy for up to 24 h after exposure, prior to cell death. In endothelial cells, exposure to 10 Gy, but not lower doses, caused a temporary increase in the transcription of genes coding for inflammatory factors before the activation of DNA damage response genes. This early inflammatory reaction depends on ATM activity, which coordinates the DNA damage response, and is not observed in blood cells or fibroblasts. Additionally, we saw an increase in cytokine production and adhesion molecule expression in endothelial cells. This inflammatory response may contribute to changes in the immune microenvironment of irradiated cells.