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저선량 감마선 노출에 의한 비장세포의 염증 유발 작용에 대한 연구

Effects of Low Dose Gamma Irradiation on the Inflammatory Response in Spleen Cells

  • 손은화 (강원대학교 생약자원개발학과)
  • Sohn, Eun-Hwa (Department of Herbal Medicine Resource, Kangwon National University)
  • 투고 : 2013.11.27
  • 심사 : 2013.12.23
  • 발행 : 2013.12.30

초록

Gamma irradiation (${\gamma}IR$) is widely used for radiotherapy as a treatment of cancer cells although it has a risk to damage normal cells. Inflammation is regarded as one of side effects of ${\gamma}IR$ while the effect of low dose of ${\gamma}IR$ on inflammation has not been researched well. Here, we investigated the inflammatory responses of low dose of ${\gamma}IR$ on murine spleen cells. It was evaluated if ${\gamma}IR$ affected the mitogen-induced lymphocyte proliferation, the regulation of various inflammatory cytokines (IFN-${\gamma}$, IL-2, IL-17, IL-4, IL-10), and the involvement of Ikaros and MAPK/NF-${\kappa}B$ medicated mechanism. Exposure of $^{137}Cs-{\gamma}IR$ below 2 Gy decreased the lymphocytes proliferative response to mitogens (LPS, ConA) except at the lowest dose, 0.05 Gy. IL-17, IL-2 and IL-4 mRNA increased at 0.5 and 2 Gy, but not altered at 0.05 Gy. IL-10, anti-inflammatory cytokine, increased only at 0.05 Gy. In regard to intracellular signaling, p-JNK, p-p38 and p-$I{\kappa}B{\alpha}$ were not changed, whereas the activation of ERK and Ikaros increased at the lowest dose. These results suggest that exposure of ${\gamma}IR$ less than 0.5 Gy (or below 0.05 Gy) has beneficial effects as a radiation hormesis on immune function.

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참고문헌

  1. Kerr, G. D., S. D. Egbert, I. Al-Nabulsi, H. L. Beck, H. M. Cullings, S. Endo, M. Hoshi, T. Imanaka, D. C. Kaul, S. Maruyama, G. I. Reeves, W. Ruehm, A. Sakaguchi, S. L. Simon, G. D. Spriggs, D. O. Stram, T. Tonda, J. F. Weiss, R. L. Weitz, and R. W. Young (2013) Workshop report on atomic bomb dosimetry-residual radiation exposure: recent research and suggestions for future studies. Health Phys. 105: 140-149. https://doi.org/10.1097/HP.0b013e31828ca73a
  2. Shahbazi-Gahrouei, D., M. Gholami, and S. Setayandeh (2013) A review on natural background radiation. Adv. Biomed. Res. 2: 65. https://doi.org/10.4103/2277-9175.115821
  3. Zhao, W. and M. E. Robbins (2009) Inflammation and chronic oxidative stress in radiation-induced late normal tissue injury: Therapeutic implications. Curr. Med. Chem. 16: 130-143. https://doi.org/10.2174/092986709787002790
  4. Singh, A. and H. Singh (1982) Time-scale and nature of radiationbiological damage: approaches to radiation protection and postirradiation therapy. Prog. Biophys. Mol. Biol. 39: 69-107. https://doi.org/10.1016/0079-6107(83)90014-7
  5. Fridovich, I. (1986) Biological effects of the superoxide radical. Arch. Biochem. Biophys. 247: 1-11. https://doi.org/10.1016/0003-9861(86)90526-6
  6. Halliwell, B. and J. M. Gutteridge (1984) Oxygen toxicity, oxygen radicals, transition metals and disease. Biochem. J. 219: 1-14. https://doi.org/10.1042/bj2190001
  7. Mirzayans, R., B. Andrais, A. Scott, Y. W. Wang, D. Murray (2013) Ionizing Radiation-Induced Responses in Human Cells with Differing TP53 Status. Int. J. Mol. Sci. 14: 22409-22435. https://doi.org/10.3390/ijms141122409
  8. Panganiban, R. A., A. L. Snow, and R. M. Day (2013) Mechanisms of radiation toxicity in transformed and non-transformed cells. Int. J. Mol. Sci. 14: 15931-15958. https://doi.org/10.3390/ijms140815931
  9. Wojcik, A., E. Gregoire, I. Hayata, L. Roy, S. Sommer, G. Stephan, and P. Voisin (2004) Cytogenetic damage in lymphocytes for the purpose of dose reconstruction: a review of three recent radiation accidents. Cytogenet. Genome. Res. 104: 200-205. https://doi.org/10.1159/000077489
  10. Luckey, T. D. (1982) Physiological benefits from low levels of ionizing radiation. Health Phys. 43: 771-789. https://doi.org/10.1097/00004032-198212000-00001
  11. Nambi, K. S. and S. D. Soman (1987) Environmental radiation and cancer in India. Health Phys. 52: 653-657. https://doi.org/10.1097/00004032-198705000-00018
  12. Bloom, E. T., M. Akiyama, Y. Kusunoki, and T. Makinodan (1987) Delayed effects of low-dose radiation on cellular immunity in atomic bombsurvivors residing in the United States. Health Phys. 52: 585-591. https://doi.org/10.1097/00004032-198705000-00009
  13. Hildebrandt, G., M. P. Seed, C. N. Freemantle, C. A. Alam, P. R. Colville-Nash, and K. R. Trott (1998) Mechanisms of the antiinflammatory activity of low-dose radiation therapy. Int. J. Radiat. Biol. 74: 367-378. https://doi.org/10.1080/095530098141500
  14. Finkel, T. (1998) Oxygen radicals and signaling. Curr. Opin. Cell Biol. 10: 248-253. https://doi.org/10.1016/S0955-0674(98)80147-6
  15. Rhee, S. G. (1999) Redox signaling: hydrogen peroxide as intracellular messenger. Exp. Mol. Med. 31: 53-59. https://doi.org/10.1038/emm.1999.9
  16. Macklis, R. M. and B. Beresford (1991) Radiation hormesis. J. Nucl. Med. 32: 350-359.
  17. Modiano, J. F., J. Mayor, C. Ball, C. G. Chitko-McKown, N. Sakata, J. Domenico-Hahn, J. J. Lucas, E. W. Gelfand (1999) Quantitative and qualitative signals determine T-cell cycle entry and progression. Cell Immunol. 197: 19-29. https://doi.org/10.1006/cimm.1999.1563
  18. Craddock, D. and A. Thomas (2006) Cytokines and late-life depression. Essent. Psychopharmacol. 7: 42-52.
  19. Misson, D. R., D. R. Abdalla, A. M. Borges, D. S. Shimba, S. J. Adad, M. A. Michelin, and E. F. Murta (2011) Cytokine serum levels in patients with cervical intraepithelial neoplasia grade II-III treated with intralesional interferon-$\alpha2b$. Tumori. 97: 578-584. https://doi.org/10.1177/030089161109700507
  20. Zou, W. and N. P. Restifo (2010) T(H)17 cells in tumor immunity and immunotherapy. Nat. Rev. Immunol. 10: 248-256. https://doi.org/10.1038/nri2742
  21. Andersen, M. H., J. Gehl, S. Reker, L. O. Pedersen, J. C. Becker, P. Geertsen, and P. Straten (2003) Dynamic changes of specific T cell responses to melanoma correlate with IL-2 administration. Semin. Cancer Biol. 13: 449-459. https://doi.org/10.1016/j.semcancer.2003.09.009
  22. Fiorentino, D. F., A. Zlotnik, P. Vieira, T. R. Mosmann, M. Howard, K. W. Moore, and A. O'Garra (1991) IL-10 acts on the antigenpresenting cell to inhibit cytokine production by Th1 cells. J. Immunol. 146: 3444-3451.
  23. Homey, B., M. Steinhoff, T. Ruzicka, and D. Y. Leung (2006) Cytokines and chemokines orchestrate atopic skin inflammation. J. Allergy Clin. Immunol. 118: 178-189. https://doi.org/10.1016/j.jaci.2006.03.047
  24. Koo, H. J., S. A. Jang, K. H. Yang, S. C. Kang, S. Namkoong, T. H. Kim, D. T. Hang, and E. H. Sohn (2013) Effects of red ginseng on the regulation of cyclooxygenase-2 of spleen cells in whole-body gamma irradiated mice. Food Chem. Toxicol. 62: 839-846. https://doi.org/10.1016/j.fct.2013.10.009
  25. Rithidech, K. N., M. Tungjai, P. Reungpatthanaphong, L. Honikel, and S. R. Simon (2012) Attenuation of oxidative damage and inflammatory responses by apigenin given to mice after irradiation. Mutat. Res. 749: 29-38. https://doi.org/10.1016/j.mrgentox.2012.08.001
  26. Lin, C. C., H. L. Hsieh, R. H. Shih, P. L. Chi, S. E. Cheng, and C. M. Yang (2013) Up-regulation of COX-2/PGE2 by endothelin-1 via MAPK-dependent NF-$\kappa{B}$ pathway in mouse brain microvascular endothelial cells. Cell Commun. Signal. 11: 1-14. https://doi.org/10.1186/1478-811X-11-1
  27. Shen, L. and G. Du (2012) Lycium barbarum polysaccharide stimulates proliferation of MCF-7 cells by the ERK pathway. Life Sci. 91: 353-357. https://doi.org/10.1016/j.lfs.2012.08.012
  28. Li, Q., L. Huai, C. Zhang, C. Wang, Y. Jia, Y. Chen, P. Yu, H. Wang, Q. Rao, M. Wang, and J. Wang (2013) Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal pathways. Int. J. Hematol. 97: 617-623. https://doi.org/10.1007/s12185-013-1317-9
  29. Nichogiannopoulou, A., M. Trevisan, S. Neben, C. Friedrich, K. Georgopoulos (1999) Defects in hemopoietic stem cell activity in Ikaros mutant mice. J. Exp. Med. 190: 1201-1214. https://doi.org/10.1084/jem.190.9.1201
  30. Wu, L., A. Nichogiannopoulou, K. Shortman, and K. Georgopoulos (1997) Cell-autonomous defects in dendritic cell populations of Ikaros mutant mice point to a developmental relationship with the lymphoid lineage. Immunity. 7: 483-492. https://doi.org/10.1016/S1074-7613(00)80370-2