title: IL-17 induces radiation resistance of B lymphoma cells by suppressing p53 expression and thereby inhibiting irradiation-triggered apoptosis.
abstract: 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.
authors.affiliation: 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.
authors.forename: Qingshan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Hematology & Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Hematology & Oncology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.
authors.forename: Bizhen
authors.initials: B
authors.lastname: Yu
authors.affiliation: Immunology Institute, Mount Sinai School of Medicine, New York, NY, USA.
authors.forename: Huabao
authors.initials: H
authors.lastname: Xiong
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D018920:Coculture Techniques; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000276:immunology; D011839:Radiation, Ionizing; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D015850:Interleukin-6; D016159:Tumor Suppressor Protein p53