Li Qingshan, Xu Xin, Zhong Weijie, Du Qinghua, Yu Bizhen, Xiong Huabao
1] Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China [2] Immunology Institute, Mount Sinai School of Medicine, New York, NY, USA.
Department of Hematology & Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
Cell Mol Immunol. 2015 May;12(3):366-72. doi: 10.1038/cmi.2014.122. Epub 2014 Dec 29.
p53 is a well-known tumor suppressor. However, the regulatory mechanism(s) for p53 expression in B lymphoma cells, and the possible role of p53 in the development of the radioresistance in tumor cells are largely unknown. A human B lymphoma cell line, Karpas1106 (k1106), was used as a model of radioresistance. Apoptosis of k1106 cells was determined using flow cytometry. Expression of p53 was assessed using real time RT-PCR and western blotting. The results showed that irradiation at 8 Gy induced apoptosis in up to 40% of k1106 cells. At the same time, the irradiation markedly increased IL-6 production of the k1106 cells. When k1106 cells were cocultured with regulatory T cells (Tregs) and irradiated, the rate of apoptotic k1106 cells was significantly reduced, indicating an acquired resistance to irradiation. IL-6 derived from the irradiation-treated k1106 cells induced IL-17 expression in Tregs. The IL-17(+)Foxp3(+) T cells suppressed p53 expression in k1106 cells. Collectively, irradiated k1106 cells induce the expression of IL-17 in Tregs, which interferes with the expression of p53 protein in k1106 cells and thereby represses irradiation-triggered apoptosis in k1106 cells.
p53是一种著名的肿瘤抑制因子。然而，B淋巴瘤细胞中p53表达的调控机制以及p53在肿瘤细胞放射抗性发展中的可能作用在很大程度上尚不清楚。人B淋巴瘤细胞系Karpas1106（k1106）被用作放射抗性模型。使用流式细胞术测定k1106细胞的凋亡情况。使用实时逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法评估p53的表达。结果表明，8 Gy的辐射诱导高达40%的k1106细胞发生凋亡。同时，辐射显著增加了k1106细胞的白细胞介素-6（IL-6）产生。当k1106细胞与调节性T细胞（Tregs）共培养并接受辐射时，凋亡的k1106细胞比例显著降低，表明获得了对辐射的抗性。来自经辐射处理的k1106细胞的IL-6诱导Tregs中IL-17的表达。IL-17(+)Foxp3(+) T细胞抑制k1106细胞中p53的表达。总体而言，经辐射的k1106细胞诱导Tregs中IL-17的表达，这干扰了k1106细胞中p53蛋白的表达，从而抑制了k1106细胞中辐射触发的凋亡。
