IRF-1-mediated IFN-γ enhancement of TRAIL-induced apoptosis

TRAIL 유도 세포사멸에 있어서 IFN-γ의한 증가 기전 연구: IRF-1과의 관련성

  • Park, Sang-Youel (Bio-Safty Research Institute, Chonbuk National University) ;
  • Seol, Jae-Won (College of Veterinary Medicine, Chonbuk National University) ;
  • Lee, You-Jin (College of Veterinary Medicine, Chonbuk National University) ;
  • Kang, Seog-Jin (National Livestock Research Institute) ;
  • Kim, In-shik (Bio-Safty Research Institute, Chonbuk National University) ;
  • Kang, Hyung-sub (Bio-Safty Research Institute, Chonbuk National University) ;
  • Chae, Joon-seok (Bio-Safty Research Institute, Chonbuk National University) ;
  • Cho, Jong-Hoo (Bio-Safty Research Institute, Chonbuk National University)
  • 박상열 (전북대학교 생체안정성연구소) ;
  • 설재원 (전북대학교 수의과대학) ;
  • 이유진 (전북대학교 수의과대학) ;
  • 강석진 (축산기술연구소) ;
  • 김인식 (전북대학교 생체안정성연구소) ;
  • 강형섭 (전북대학교 생체안정성연구소) ;
  • 채준석 (전북대학교 생체안정성연구소) ;
  • 조종후 (전북대학교 생체안정성연구소)
  • Accepted : 2004.04.17
  • Published : 2004.06.30

Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family and potent inducer of apoptosis. TRAIL has been shown to effectively limit tumor growth in vivo without detectable cytotoxic side effects. Interferon (IFN)-${\gamma}$ often modulates the anti-cancer activities of TNF family members including TRAIL. We previously reported that IFN-${\gamma}$ enhanced TRAIL-induced Apoptosis in HeLa cells without the unknown mechanism. In this study, we investigated whether IRF-1 involves in IFN-${\gamma}$-enhanced TRAIL-induced apoptosis. We exposed HeLa cells to IFN-${\gamma}$ for 12 hours and then treated with recombinant TRAIL protein. No apoptosis was induced in cells pretreated with IFN-${\gamma}$, and TRAIL only induced 30% apoptosis after 3 hours treatment. In HeLa cells pretreated with IFN-${\gamma}$, TRAIL induced cell death to more than 75% at 3 hours, showed that IFN-${\gamma}$-pretreatment enhanced HeLa cell death to TRAIL-induced apoptosis. To investigate the functional role of IRF-1 in IFN-${\gamma}$-enhanced TRAIL-induced apoptosis, IRF-1 was overexpressed by using an adenoviral vector AdIRF-1. IRF-1 overexpression increased apoptotic cell death and significantly enhanced apoptotic cell death induced by TRAIL when infected cells were treated with TRAIL. Our findings show that IFN-${\gamma}$ enhances TRAIL-induced apoptosis by IRF-1 in HeLa cells.

Acknowledgement

Supported by : 전북대학교

References

  1. Harada, H., Kitagawa, M., Tanaka, N., Yamamoto, H., Harada, K., Ishihara, M. and Taniguchi, T. Antioncogenic and oncogenic potentials of interferonregulatory factors-1 and -2. Science. 1993, 259, 971-974
  2. Kakimi, K., Guidotti, L. G., Koezuka, Y. and Chisari, F. V. Natural killer T cell activation inhibits hepatitis B virus replication in vivo. J. Exp. Med. 2000, 192, 921-930
  3. Kim, K. B., Choi, Y. H., Kim, I. K., Chung, C. W., Kim, B. J., Park, Y. M. and Jung, Y. K. Potentiation of Fas- and TRAIL-mediated apoptosis by IFN-gammain A549 lung epithelial cells: enhancement of caspase-8 expression through IFN-response element. Cytokine. 2002, 20, 283-288
  4. Sasagawa, T., Hlaing, M. and Akaike, T. Synergistic induction of apoptosis in murine hepatoma Hepa1-6 cells by IFN-gamma and TNF-alpha. Biochem.Biophys. Res. Commun. 2000, 272, 674-680
  5. Seol, D. W., Li, J., Seol, M. H., Park, S. Y., Talanian, R. V. and Billiar, T. R. Signaling events triggered by tumor necrosis factor-related apoptosis- inducing ligand (TRAIL): caspase-8 is required for TRAIL-induced apoptosis. Cancer Res. 2001, 61, 1138-1143
  6. Tanaka, N., Ishihara, M., Lamphier, M. S., Nozawa, H., Matsuyama, T., Mak, T. W., Aizawa, S., Tokino,T., Oren, M. and Taniguchi, T. Cooperation of the tumour suppressors IRF-1 and p53 in response to DNA damage. Nature. 1996, 382, 816-818
  7. Zhou, Y., Wang, S., Gobl, A. and Oberg, K. The interferon-alpha regulation of interferon regulatory factor 1 (IRF-1) and IRF-2 has therapeutic implicationsin carcinoid tumors. Ann. Oncol. 2000, 11, 707-714
  8. Seol, D. W. and Billiar, T. R. Cysteine 230 modulates tumor necrosis factor-related apoptosis-inducing ligand activity. Cancer Res. 2000, 60, 3152-3154
  9. Fujita, T., Sakakibara, J., Sudo, Y., Miyamoto, M., Kimura, Y. and Taniguchi, T. Evidence for a nuclear factor(s), IRF-1, mediating induction and silencingproperties to human IFN-beta gene regulatory elements. EMBO J. 1988, 7, 3397-3405
  10. Pitti, R. M., Marsters, S. A., Ruppert, S., Donahue, C. J., Moore, A. and Ashkenazi, A. Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J. Biol. Chem. 1996, 271, 12687-12690
  11. Nunokawa, Y. and Tanaka, S. Interferon-gamma inhibits proliferation of rat vascular smooth muscle cells by nitric oxide generation. Biochem. Biophys.Res. Commun. 1992, 188, 409-415
  12. Tanaka, N., Ishihara, M. and Taniguchi, T. Suppression of c-myc or fosB-induced cell transformation by the transcription factor IRF-1. Cancer Lett. 1994, 83, 191-196
  13. Shin, E. C., Shin, W. C., Choi, Y., Kim, H., Park, J. H. and Kim, S. J. Effect of interferon-gamma on the susceptibility to Fas (CD95/APO-1)- mediated celldeath in human hepatoma cells. Cancer Immunol Immunother. 2001, 50, 23-30
  14. Cha, S. S., Kim, M. S., Choi, Y. H., Sung, B. J., Shin, N. K., Shin, H. C., Sung, Y. C. and Oh, B. H. 2.8 A resolution crystal structure of human TRAIL, acytokine with selective antitumor activity. Immunity. 1999, 11, 253-261
  15. Park, S. Y., Billiar, T. R. and Seol, D. W. IFN-g Inhibition of TRAIL-Induced IAP-2 Upregulation, a Possible Mechanism of IFN-g-Enhanced TRAILInducedApoptosis. Biochem. Biophys. Res. Commun. 2002, 291, 233-236
  16. Tanaka, N., Ishihara, M., Kitagawa, M., Harada, H., Kimura, T., Matsuyama, T., Lamphier, M. S., Aizawa, S., Mak, T. W. and Taniguchi, T. Cellularcommitment to oncogene-induced transformation or apoptosis is dependent on the transcription factor IRF-1. Cell. 1994, 77, 829-839
  17. Kirkwood, J. M., Ernstoff, M. S., Trautman, T., Hebert, G., Nishida, Y., Davis, C. A., Balzer, J., Reich, S., Schindler, J. and Rudnick, S. A. In vivo biological response to recombinant interferon-gamma during a phase I dose-response trial in patients with metastatic melanoma. J. Clin. Oncol. 1990, 8, 1070-1082
  18. Suk, K., Kim, S., Kim, Y. H., Kim, K. A., Chang, I., Yagita, H., Shong, M. and Lee, M. S. IFN-gamma/TNF-alpha synergism as the final effector inautoimmune diabetes: a key role for STAT1/IFN regulatory factor-1 pathway in pancreatic beta cell death. J. Immunol. 2001, 166, 4481-4489
  19. Hymowitz, S. G., Christinger, H. W., Fuh, G., Ultsch, M., O'Connell, M., Kelley, R. F., Ashkenazi, A. and de Vos, A. M. Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5. Mol. Cell. 1999, 4, 563-571
  20. Wiley, S. R., Schooley, K., Smolak, P. J., Din, W. S., Huang, C. P., Nicholl, J. K., Sutherland, G. R., Smith, T. D., Rauch, C. and Smith, C. A. Identificationand characterization of a new member of the TNF family that induces apoptosis. Immunity. 1995, 3, 673-682
  21. Fujita, T., Kimura, Y., Miyamoto, M., Barsoumian,E. L. and Taniguchi, T. Induction of endogenous IFNalpha and IFN-beta genes by a regulatory transcription factor, IRF-1. Nature. 1989, 337, 270-272
  22. Nagata, S. Apoptosis by death factor. Cell. 1997, 88, 355-365
  23. Park, S. Y., Billiar, T. R. and Seol, D. W. Hypoxia Inhibition of Apoptosis Induced by Tumor Necrosis Factor- Related Apoptosis-Inducing Ligand (TRAIL).Biochem. Biophys. Res. Commun. 2002, 291, 150-153
  24. Yang, X., Merchant, M. S., Romero, M. E., Tsokos, M., Wexler, L. H., Kontny, U., Mackall, C. L. and Thiele, C. J. Induction of caspase 8 by interferon gamma renders some neuroblastoma (NB) cells sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but reveals that a lack of membraneTR1/TR2 also contributes to TRAIL resistance in NB. Cancer Res. 2003, 63, 1122-1129
  25. Fish, S. M., Proujansky, R. and Reenstra, W. W. Synergistic effects of interferon gamma and tumour necrosis factor alpha on T84 cell function. Gut. 1999, 45, 191-198
  26. Tamura, T., Ishihara, M., Lamphier, M. S., Tanaka, N., Oishi, I., Aizawa, S., Matsuyama, T., Mak, T. W., Taki, S. and Taniguchi, T. An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogenactivated T lymphocytes. Nature. 1995, 376, 596-599
  27. Hardy, S., Kitamura, M., Harris-Stansil, T., Dai, Y. and Phipps, M. L. onstruction of adenovirus vectors through Cre-lox recombination. J. Virol. 1997, 71, 1842-1849
  28. Park, S. Y. and Seol, D. W. Regulation of Akt by EGF-R inhibitors, a possible mechanism of EGF-R inhibitor-enhanced TRAIL-induced apoptosis. BiochemBiophys. Res. Commun. 2002, 295, 515-518
  29. Taniguchi, T., Lamphier, M. S. and Tanaka, N. IRF- 1: the transcription factor linking the interferon response and oncogenesis. Biochim. Biophys. Acta. 1997, 1333, M9-17
  30. Kirkwood, J. M. and Ernstoff, M. S. Role of interferons in the therapy of melanoma. J. Invest. Dermatol. 1990, 95, 180S-184S
  31. Orange, J. S., Wolf, S. F. and Biron, C. A. Effects of IL-12 on the response and susceptibility to experimental viral infections. J. Immunol. 1994, 152, 1253-1264
  32. Tamura, T., Ishihara, M., Lamphier, M. S., Tanaka, N., Oishi, I., Aizawa, S., Matsuyama, T., Mak, T. W., Taki, S. and Taniguchi, T. DNA damage-inducedapoptosis and Ice gene induction in mitogenically activated T lymphocytes require IRF-1. Leukemia. 1997, 11 Suppl 3, 439-440