Skip to main content
Log in

Upregulation of Fas-induced apoptosis by interferon-γ accompanied by increased ICE expression in renal cell cancer cells

  • Reports
  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

The integration of Fas/Apo-1 (CD95) by Fas ligand or anti-Fas antibody induces apoptosis, and this system plays a pivotal role for the lysis of target cells by cytotoxic T lymphocytes. Fas-mediated apoptosis is also increased by a prior incubation of Fas-bearing cells with interferon(IFN)-γ. Interleukin-1-β converting enzyme (ICE) and/or CPP32, or other members of ICE family act as direct cell death executors downstream of this mechanism, and a tetrapeptide inhibitor of these cysteine proteases blocks Fas-mediated apoptosis. In this study, we examined the effect of IFN-γ on Fas-mediated apoptosis in ACHN cells. IFN-γ augmented apoptosis in a dose dependent manner and reached a plateau at 400 U/ml when exposed for 48 h before the end of culture. The kinetics revealed a significant increase in apoptosis after 24 h. Exposing ACHN cells to IFN-γ increased pro-ICE expression accompanied with a decrease of pro-CPP32. These results suggest that direct enhancement of ICE expression and/or upregulation of conversion of pro-CPP32 to active form increases Fas-mediated apoptosis by IFN-γ in ACHN cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Ju ST, Panka DJ, Cui H,et al. Fas (CD95)/FasL interactions required for programmed cell death after T-cell activation.Nature 1995;373: 444–448.

    PubMed  Google Scholar 

  2. Nagata S, Golstein P. The Fas death factor.Science 1995;267: 1449–1456.

    PubMed  Google Scholar 

  3. Yonehara S, Ishii A, Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor.J Exp Med 1989;169: 1747–1756.

    PubMed  Google Scholar 

  4. Tamura T, Ishihara M, Lamphier MS,et al. An IRF-1-dependent pathway of DNA damage-induced apoptosis in mitogen-activated T lymphocytes.Nature 1995;376: 596–599.

    PubMed  Google Scholar 

  5. Pine R, Canova A, Schindler C. Tyrosine phosphorylated p91 binds to a single element in the ISGF2/IRF-1 promoter to mediate induction by IFNα and IFNγ, and is likely to autoregulate the p91 gene.EMBO J 1994;13: 158–167.

    PubMed  Google Scholar 

  6. Tomita Y, Kawasaki T, Bilim V, Takeda M, Takahashi K. Tetrapeptide DEVD-aldehyde or YVAD-chloromethylketone Inhibits Fas/Apo-1 (CD95)-mediated apoptosis in renal cell cancer cells.Int J Cancer 1996;68: 132–135.

    PubMed  Google Scholar 

  7. Tomita Y, Bilim V, Kawasaki T,et al. Frequent expression of Bcl-2 in renal cell carcinomas carrying wild-type p53.Int J Cancer 1996;66: 322–325.

    PubMed  Google Scholar 

  8. Williams MS, Henkart PA. Apoptotic cell death induced by intracellular proteolysis.J Immunol 1994; 153: 4247–4255.

    PubMed  Google Scholar 

  9. Yagoda A. Chemotherapy of renal cell carcinoma: 1983–1989.Semin Urol 1989;7: 199–202.

    Google Scholar 

  10. Forman JD. The role of radiation therapy in the management of carcinoma of the kidney.Semin Urol 1989;7: 195–198.

    PubMed  Google Scholar 

  11. Savage PD. Renal cell carcinoma.Curr Opin Oncol 1995;7: 275–280.

    PubMed  Google Scholar 

  12. Montel AH, Bochan MR, Hobbs JA, Lynch DH, Brahmi Z. Fas involvement in cytotoxicity mediated by human NK cells.Cell Immunol 1995;166: 236–246.

    PubMed  Google Scholar 

  13. Enari M, Hug H, Nagata S. Involvement of an ICE-like protease in Fas-mediated apoptosis.Nature 1995;375: 78–81.

    PubMed  Google Scholar 

  14. Schlegel J, Peters I, Orrenius S,et al. CPP32/apopain is a key interleukin l β-converting enzyme-like protease involved in Fas-mediated apoptosis.J Biol Chem 1996;271: 1841–1844.

    PubMed  Google Scholar 

  15. Nicholson DW, Ali A, Thornberry NA,et al. Identification and inhibition of the ICE/CPD-3 protease necessary for mammalian apoptosis.Nature 1995;376: 37–43.

    PubMed  Google Scholar 

  16. Shresta S, Heusel JW, Macivor DM, Wesselschmidt RL, Russell JH, Ley TJ. Granzyme B plays a critical role in cytotoxic lymphocyte-induced apoptosis.Immunol Rev 1995;146: 211–221.

    PubMed  Google Scholar 

  17. Darmon AJ, Nicholson DW, Bleackley RC. Activation of the apoptotic protease CPP32 by cytotoxic T-cell-derived granzyme B.Nature 1995;377: 446–468.

    PubMed  Google Scholar 

  18. Lazebnik YA, Kaufmann SH, Desnoyers S, Poirier GG, Earnshaw WC. Cleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE.Nature 1994;371: 346–347.

    PubMed  Google Scholar 

  19. Tewari M, Quan LT, O'Rourke K,et al. Yama/CPP32 β, a mammalian homolog of CED-3, is a CrmA-inhibitable pro tease that cleaves the death substrate poly(ADP-ribose) polymerase.Cell 1995;81: 801–809.

    PubMed  Google Scholar 

  20. Li P, Allen H, Banerjee S,et al. Mice deficient in IL-1 β-converting enzyme are defective in production of mature IL-1 β and resistant to endotoxic shock.Cell 1995;80: 401–411.

    PubMed  Google Scholar 

  21. Kuida K, Lippke JA, Ku G,et al. Altered cytokine export and apoptosis in mice deficient in interleukin-1 β converting enzyme.Science 1995;267: 2000–2003.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tomita, Y., Bilim, V., Takeda, M. et al. Upregulation of Fas-induced apoptosis by interferon-γ accompanied by increased ICE expression in renal cell cancer cells. Apoptosis 1, 209–212 (1996). https://doi.org/10.1007/BF01321104

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01321104

Key words

Navigation