KIRAMS / 강아람, 박종국*
Abstract
Here, we demonstrate that interleukin-1β (IL-1β) contributes to the γ-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-1β were increased upon exposure of A549 cells to IR. We then demonstrated that IR-induced IL-1β is located downstream of the NF-κB-RIP1 signaling pathway. Treatments with siRNA and specific pharmaceutical inhibitors of RIP1 and NF-κB suppressed the IR-induced increases in the protein expression and secreted concentration of IL-1β. IL-1Ra, an antagonist of IL-1β, treatment suppressed the IR-induced epithelial-mesenchymal transition (EMT) and IR-induced invasion/migration in vitro. These results suggest that IL-1β could regulate IR-induced EMT. We also found that IR could induce the expression of IL-1β 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-1β suggest that an autocrine loop between IL-1β 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-κB and RIP1 to trigger the NF-κB-RIP1-IL-1β-IL-1RI/II-EMT pathway, ultimately promoting metastasis.
Affiliations
A-Ram Kang 1 , Jeong Hyun Cho 1 , Na-Gyeong Lee 1 , Jin-Hee Kwon 1 , Jie-Young Song 1 , Sang-Gu Hwang 1 , In Su Jung 2 , Jae-Sung Kim 1 , Hong-Duck Um 1 , Sang Cheul Oh 3 , Jong Kuk Park 4
1 Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Republic of Korea.
2 Medical Accelerator Team, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Republic of Korea.
3 Department of Oncology, Korea University Guro Hospital, Seoul, 08308, Republic of Korea.
4 Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, Republic of Korea. Electronic address: jkpark@kirams.re.kr.