IL-17 induces radiation resistance of B lymphoma cells by suppressing p53 expression and thereby inhibiting irradiation-triggered apoptosis

Cell Mol Immunol. 2015 May;12(3):366-72. doi: 10.1038/cmi.2014.122. Epub 2014 Dec 29.

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.

MeSH terms

  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • Coculture Techniques
  • Down-Regulation
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Interleukin-17 / metabolism*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / radiotherapy
  • Radiation Tolerance / immunology
  • Radiation, Ionizing
  • T-Lymphocytes, Regulatory / immunology*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Interleukin-17
  • Interleukin-6
  • Tumor Suppressor Protein p53