Abstract
The tryptophan catabolic enzyme, indoleamine 2,3 dioxygenase (IDO), has been shown to be induced in vivo in lungs of mice by bacterial lipopolysaccharide (Yoshida and Hayaishi, 1978), by influenza virus (Yoshida et al., 1979) and by IFN-gamma (IFN-γ) (Carlin et al., 1987, Taylor and Feng 1991). Unlike other interferon responsive genes, this enzyme is not appreciably induced by any of the type I interferons. We (Feng and Taylor 1989) have previously reported that the human cell line ME180 undergoes cell death very rapidly following treatment with IFN-γ. This cell death appears to be the result of starvation for the essential amino acid tryptophan due to the induction of IDO (Feng and Taylor 1989, Ozaki et al., 1988, Aune and Pogue 1989). In ME180 mutants resistant to the antiproliferative effects of IFN-γ, there is no induction of IDO (Feng and Taylor 1989). Moreover the antiproliferative response to IFN-γ can be reversed by the addition of tryptophan back to the medium (Feng and Taylor, 1989, Ozes and Taylor 1993). In this paper we report that the antiproliferative response to IFN-γ results in apoptosis of treated cells, and that tryptophan starvation by itself appears to be sufficient to drive the cell to apoptosis through the same or similar mechanism.
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References
Aune, T.M., and Pogue, S.L., 1989, Inhibition of tumor cell growth by interferon gamma is mediated by two distinct mechanism dependent upon oxygen tension: induction of tryptophan degradation in vitro and depletion of intracellular nicotinamide adenine dinucleotide. J. Clinical Invest.84: 863
Carlin, J.M., Borden, E.C., Sondel, P.M. and Byrne, G.I., 1987, Biological Response modifier-induced indoleamine 2,3 dioxygenase activity in human peripheral blood mononuclear cell cultures. J. Immunol139: 2414
Chen, M., Quintans, J., Fuks, Z., Thompson, C., Kufe, D.W., and Weichselbaum, R.R., 1995, Suppression of Bcl-2 messenger RNA production may mediate apoptosis after ionizing radiation, tumor necrosis factor -a, and ceramide. Cancer Research55: 991
Chong, K.L., Feng, L., Schappert, K., Meurs, E., Donahue, T.F., Freisen, D.J., Havanessian, A.G., and Williams, B.R., 1992, Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2. EMBO-J., 11: 1553
Feng, G., and Taylor, M.W., 1989, Interferon-y resistant mutants are defective in the induction of indoleamine 2,3 dioxygenase. Proc. Natl Acad. Sci. USA86: 7144
Lee, S.B., and Esteban, M., 1994, The interferon induced double-stranded RNA activated protein kinase induces apoptosis. Virology199: 491
McCormack, S.J., Ortega, L.G., Doohan, J.P., and Samuel, C.E., 1994, Mechanisms of interferon action motif I of the interferon induced, RNA-dependent protein kinase (PKR) is sufficient to mediate RNA-bind- ing activity. Virology, 198: 92
Muschel, R.J., Berahard, E.J., Garza, L., McKenna, W.G., and Koch, C.J., 1995, Induction of apoptosis at different oxygen tensions. Evidence that oxygen radicals do not mediate apoptotic signaling. Cancer Research, 55: 995
Ozaki, Y., Edelstein, M.P., and Duch, D.S., 1988, Induction of indoleamine 2,3 dioxygenase: a mechanism of the antitumor activity of interferon-γ. Proc. Nat. Acad. Sci USA85: 1242
Ozes, O.N., and Taylor, M.W., 1993, Reversal of IFN-γ resistant phenotype by polyI:C. Possible involvement of double stranded RNA activated kinase in IFN-γ mediated induction of the IDO gene. J. Interferon Research.13: 283
Samuel, C.E., 1993, The eIF-2 alpha protein kinases, regulators of translation in eukaryotes and yeasts to humans. J. Biol Chem.268: 7603
Taylor, M.W., and Feng, G., 1991, relationship between interferon-γ, indoleamine 2,3 dioxygenase and tryptophan catabolism. FASEB J. 5: 2516
Wagner, A.J., Small, M.B., and Hay, N., 1993, Myc-mediated apoptosis is blocked by ectopic expression of Bcl-2. Mol. Cell Biol13: 2432
Yoshida, R., and Hayaishi, O., 1978, Induction of pulmonary indoleamine 2,3 dioxygenase by intraperitoneal injection of bacterial lipopolysaccharide. Proc. Nat. Acad. Sci. USA75: 3998
Yoshida, R., Urade, Y., Tokuda, M., and Hayaishi, O., 1979, Induction of indoleamine 2,3 dioxygenase in mouse lung during virus infection. Proc. Nat. Acad. Sci. USA76: 4084
Yonish-Rouach, E. Resnitzky, D., Lotem, J., Sachs, L., Kimchi, A., and Oren, M., 1991, Wild type p53 induces apoptosis of myeloid leukemic cells that is inhibited by interleukin-6. Nature352: 345
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© 1996 Plenum Press, New York
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Taylor, M.W., Konan, V.K., Yu, D. (1996). Tryptophan Starvation is Involved in Human Interferon-Gamma Mediated Apoptosis. In: Filippini, G.A., Costa, C.V.L., Bertazzo, A. (eds) Recent Advances in Tryptophan Research. Advances in Experimental Medicine and Biology, vol 398. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0381-7_25
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DOI: https://doi.org/10.1007/978-1-4613-0381-7_25
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