PMID: 2506547Sep 1, 1989Paper

Interferon gamma-resistant mutants are defective in the induction of indoleamine 2,3-dioxygenase

Proceedings of the National Academy of Sciences of the United States of America
G S Feng, M W Taylor

Abstract

Several mutants of the human cell line ME-180 resistant to the cytotoxic effect of interferon gamma (IFN-gamma) were isolated after mutagenesis with nitrosoguanidine. Two of the mutant lines (ME-IR3b and ME-IR6g) examined had significantly lower induction levels of the L-tryptophan (L-Trp) degradative enzyme indoleamine 2,3-dioxygenase activity in response to IFN-gamma. Moreover, culture medium supplemented with low concentrations of L-Trp reversed the cytotoxic effect of IFN-gamma, whereas higher concentrations of L-Trp in the medium were extremely toxic to both parental and mutant cells. These mutants were still protected against herpes simplex virus infection by IFN-gamma and expressed the HLA-DR alpha gene normally in the presence of this lymphokine. Thus, the mutation in these cells is specific to indoleamine 2,3-dioxygenase and not a global effect of an IFN-gamma-induced gene. This genetic evidence indicates that the major pathway of IFN-gamma cytotoxicity in this cell line is mediated primarily by induction of indoleamine 2,3-dioxygenase and deprivation of L-Trp.

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Citations

Jan 12, 1994·Journal of Immunological Methods·W DäubenerU Hadding
Jun 1, 1997·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·F BurkeF R Balkwill
Mar 14, 2000·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·M X DuM W Taylor
Aug 5, 2000·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·W D Sotero-EstevaM W Taylor
Dec 1, 1994·Journal of Interferon Research·S B KleinM W Taylor
Feb 1, 1995·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·T OhtaM Kurimoto
Jul 1, 1996·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·W DäubenerU Hadding
Sep 1, 1996·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·K V Konan, M W Taylor
Sep 10, 2003·American Journal of Respiratory Cell and Molecular Biology·Kena A SwansonDavid S Wilkes
Sep 3, 2003·Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society·Kourosh SarkhoshAziz Ghahary
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Dec 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthijs van WissenRené Lutter
May 16, 2019·Journal of Zhejiang University. Science. B·Gen-Sheng Feng

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