Here, we demonstrate that interleukin-1 beta (IL-1 beta) contributes to the gamma-ionizing radiation (IR)-induced increase of migration/invasion in A549 lung cancer cells, and that this occurs via RIP1 upregulation. We initially observed that the protein expression and secreted concentration of IL-1 beta were increased upon exposure of A549 cells to IR. We then demonstrated that IR-induced IL-1 beta is located downstream of the NF-kappa B-RIP1 signaling pathway. Treatments with siRNA and specific pharmaceutical inhibitors of RIP1 and NF-kappa B suppressed the IR-induced increases in the protein expression and secreted concentration of IL-1 beta. IL-1R alpha, an antagonist of IL-1 beta, treatment suppressed the IR-induced epithelial-mesenchymal transition (EMT) and IR-induced invasion/migration in vitro. These results suggest that IL-1 beta could regulate IR-induced EMT. We also found that IR could induce the expression of IL-1 beta expression in vivo and that of IL-1 receptor (R) I/II in vitro and in vivo. The IR-induced increases in the protein levels of IL-1 RI/II and IL-1 beta suggest that an autocrine loop between IL-1 beta and IL-1 RI/II might play important roles in IR-induced EMT and migration/invasion. Based on these collective results, we propose that IR concomitantly activates NF-kappa B and RIP1 to trigger the NF-kappa B-RIP1-IL-1 beta-IL-1RI/II-EMT pathway, ultimately promoting metastasis. (c) 2020 Elsevier Inc. All rights reserved.