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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Gamma Irradiation-reduced IFN-γ Expression, STAT1 Signals, and Cell-mediated Immunity

  • Han, Seon-Kyu (Laboratory of Immunology, Korea Cancer Center Hospital) ;
  • Song, Jie-Young (Laboratory of Immunology, Korea Cancer Center Hospital) ;
  • Yun, Yeon-Sook (Laboratory of Immunology, Korea Cancer Center Hospital) ;
  • Yi, Seh-Yoon (Laboratory of Immunology, Korea Cancer Center Hospital)
  • Published : 2002.11.30
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Abstract

The signal transducer and activator of transcription (STAT)1 is a cytoplasmic-transcription factor that is phosphorylated by Janus kinases (Jak) in response to interferon $\gamma$ (IFN-$\gamma$). The phosphorylated STAT1 translocates to the nucleus, where it turns on specific sets of IFN-$\gamma$-inducible genes, such as the interferon regulatory factor (IRF)-1. We show here that gamma irradiation reduces the IFN-$\gamma$ mRNA expression. The inhibition of the STAT1 phosphorylation and the IRF-1 expression by gamma irradiation was also observed. In contrast, the mRNA levels of IL-5 and transcription factor GATA-3 were slightly induced by gamma irradiation when compared to the non-irradiated sample. Furthermore, we detected the inhibition of cell-mediated immunity by gamma irradiation in the allogenic-mixed lymphocytes' reaction (MLR). These results postulate that gamma irradiation induces the polarized-Th2 response and interferes with STAT1 signals, thereby causing the immunosuppression of the Th1 response.

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References

  1. Aragane, Y., Kulms, D., Luger, T. A. and Schwartz, T. (1997) Down-regulation of interferon g-activated STAT1 by UV light. Proc. Natl, Acad. Sci. USA 94, 11490-11495. https://doi.org/10.1073/pnas.94.21.11490
  2. Aruga, A., Aruga, E., Tanigawa, K., Bishop, D. K., Sondak, V. K. and Chang, A. E. (1997) Type I versus type 2 cytokine release by Vb T cell subpopulations determines in vivo antitumor reactivity: IL-10 mediates a suppressive role. J. Immunol. 159, 664-673.
  3. Chapman, R. S., Cooper, K. D., DeFabo, E. C., Frederich, J. E. and Gelatt, K. N. (1995) Solar ultraviolet radiation and the risk of infectious disease: summary of a workshop. Photochem. Phorobiol. 61, 223-247. https://doi.org/10.1111/j.1751-1097.1995.tb03966.x
  4. Cho, H. Y., Kim, W. J., Lee, S. W., Kim, Y. M., Choi, E. Y., Park, Y. S., Kwon, Y. G. and Kim, K. W. (2001) Anti-augioqenic activity of mouse N-IC-terminal deleted endostation, J. Biochem. Mol. Biol. 34, 206-211.
  5. Coccia, E. M., Passini, N., Battistini, A., Oini, C., Sinigaglia, F. and Rogge, L. (1999) Interleukin-12 induces expression of interferon regulatory factor-1 via signal transducer and activator of transcription-4 in human T helper type 1 cells. J. BioI. Chem. 274, 6698-6703. https://doi.org/10.1074/jbc.274.10.6698
  6. Farrar, M. A. and Schreiber, R. D. (1993) The molecular cell biology of interferon-gamma and its receptor. Annu. Rev. Imnunnol. 11, 571-611. https://doi.org/10.1146/annurev.iy.11.040193.003035
  7. Galdiero, M., Cipollaro del'Ero, G., Folgore, A., Cappello, M., Giobbe, A. and Sasso, F. S. (1994) Effects of irradiation doses on alteration in cytokine release by monocytes and lymphoeytes. J. Med. 25, 23-40.
  8. Greenlund, A. C., Farrar, M. A., Viviano, B. L. and Schreiber, R. D. (1994) Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91). EMBO J. 13, 1591-1600.
  9. Greenlund, A. C., Morales, M. O., Viviano, B. L., Yan, H., Krolewski, J. and Schreiber, R. D. (1995) Stat recruitment by tyrosine-phosphorylated cytokine receptors: an ordered reversible affinity-driven process. Immunity 2, 677-687. https://doi.org/10.1016/1074-7613(95)90012-8
  10. Harada, H., Fujita, T., Miyamoto, M., Kumura, T., Maruyama, M., Furla, A., Miyata, T. and Taniguchi, T. (1989) Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell 58, 729-739. https://doi.org/10.1016/0092-8674(89)90107-4
  11. Haspel, R. L., Salditt-Georgieff, M. and Damell, J. E. (1996) The rapid inactivation of nuclear tyrosine phosphorylated STAT1 depends upon a protein tyrosine phosphatase. EMRO J. 15, 6262-6268.
  12. Kim, J. I., Ho, I. C., Grusby, M. J. and Glimcher, L. H. (1999) The transcription factor c-Maf controls the production of interleukin-4 but not other Th2 cytokines. Immunity 10, 745- 751. https://doi.org/10.1016/S1074-7613(00)80073-4
  13. Kripke, M. L. (1990) Photoimmunology. Photochem. Photobiol. 52, 919-924. https://doi.org/10.1111/j.1751-1097.1990.tb08703.x
  14. Lee, C. K., Bluyssen, H. A. R. and Levy, D. E. (1997) Regulation of interferon-a responsiveness by the duration of Janus Kinase activity. J. Biol. Chem. 272, 21872-21877. https://doi.org/10.1074/jbc.272.35.21872
  15. Lohoff, M., Ferricd, K., Mittrucker, H. W., Duncan, G. S., Bischoff, S., Rollinghoff, M. and Mak, T. W. (1997) Interferon regulatory factor-1 is required for a T helper 1 immune response in vivo. Immunity 6, 681-689. https://doi.org/10.1016/S1074-7613(00)80444-6
  16. Ouyang, W., Ranganath, S. H., Weindel, K., Bhattacharya, D., Murphy, T. L., Sha, W. C. and Murphy, K. M. (1998) Inhibition of Th1 development mediated by GATA-3 through an IL-4 independent mechanism. Immunity 9, 745-755. https://doi.org/10.1016/S1074-7613(00)80671-8
  17. Pine, R., Canova, A. and Schindler, C. (1994) Tyrosine phosphorylated p91 binds to a single element in the ISGF2/ IRP-1 promoter to mediate induction by IFN alpha and IFN gamma, and is likely to autoregulate the p91 gene. EMBO J. 13, 158-167.
  18. Sakatsume, M., Igarushi, K., Winestock, K. D., Garotta, G., Larner, A. C. and Finbloom, D. S. (1995) The Jak kinases differentially associate with the alpha and beta (accessory factor) chains of the interferon gamma receptor to form a functional receptor unit capable of activating STAT transcription factors. J. Biol. Chem. 270, 17528-17534. https://doi.org/10.1074/jbc.270.29.17528
  19. Sato, T., Selleri, C., Young, N. S. and Maciejewski, J. P. (1997) Inhibition of Interferon regulatory factor-1 expression results in predominance of cell growth stimulatory effects of interferon-g due to phosphorylation of Stat1 and Stat3. Blood 90, 4749-4758.
  20. Shuai, K., Stark, G. R., Kerr, I. M. and DarnelI, J. E. (1993) Polypeptide signaling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Nature 366, 580-583. https://doi.org/10.1038/366580a0
  21. Silennoinen, O., Ihle, J. N., Schlessinger, J. and Levy, D. E. (1993) Interferon-induced nuclear signaling by Jak protein tyrosine kinase. Nature 366, 583-585. https://doi.org/10.1038/366583a0
  22. Szabo, S. J., Jacobson, N. G., Dighe, A. S., Gubler, U. and Murphy, K. M. (1995) Developmental commitment to the Th2 lineage by extinction of IL-12 signaling. Immunity 2, 665-675. https://doi.org/10.1016/1074-7613(95)90011-X
  23. Taki, S., Sato, T., Ogasawara, K., Fukuda, T., Sato, M., Hida, S., Suzuki, G., Mitsuyama, M., Shin, E. H., Kojima, S., Taniguchi, T. and Asano, Y. (1997) Multistage regulation of Th1-type immune response by the transcription factor IRF-1. Immunity 6, 673-679. https://doi.org/10.1016/S1074-7613(00)80443-4
  24. Tepper, R. I., Coffman, R. L. and Leder, P. (1992) An eosinophil-dependent mechanism for the antitumor effect of interleukin-4. Science 257, 548-551. https://doi.org/10.1126/science.1636093
  25. Watowich, S. S., Wu, H., Socolovsky, M., KlingmuIler, U., Constantinescu, S. N. and Lodish, H. F. (1996) Cytokine receptor signal transduction and the control of hematopoietic cell development. Annu. Rev. Cell. Dev. Biol. 12, 91-128. https://doi.org/10.1146/annurev.cellbio.12.1.91
  26. Yi, J. Y., Hong, W. S. and Son, Y. S. (2001) Biochemical Characterization of Adriamycin-resistance in PC-14 human Lung Adenocarcinoma Cell Line. J. Biochem. Mol. Biol. 34, 66-72.
  27. Yoshimori, A., Agatha, S., Thomas, A. L., Kiyoshi, A., Akira, T., and Thomas, S. (1997) Ultraviolet light suppress IFN-$\gamma$-induced IL-7 gene expression in Murine keratinocytes by interfering with IFN regulatory Factors. J. Immunol. 158, 5393-5399.
  28. Zhang, D. H., Cohn, L., Ray, P., Bottomly, K. and Ray, A. (1997) Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J. Biol. Chem. 272, 21597-21603. https://doi.org/10.1074/jbc.272.34.21597

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