Abstract
Human normal and malignant T cells cease to proliferate, down-modulate Bcl-2 expression, and undergo apoptosis when cultured in the presence of NO-donor compounds (sodium nitroprusside and NOC12) for 48 h. At 72 h, cells that evade apoptosis start to proliferate again, overexpress both chains of the IFN-gammaR, and thus become susceptible to apoptosis in the presence of IFN-gamma. By contrast, in the presence of IFN-gamma, no apoptosis, but an increase of proliferation was displayed by control cultures of T cells not exposed to NO and not overexpressing IFN-gammaR chains. The NO-induced cell surface overexpression of IFN-gammaR chains did not affect the transduction of IFN-gamma-mediated signals, as shown by the expression of the transcription factor IFN regulatory factor 1 (IRF-1). However, transduction of these signals was quantitatively modified, because IFN-gamma induces enhanced levels of caspase-1 effector death in NO-treated cells. These findings identify NO as one of the environmental factors that critically govern the response of T cells to IFN-gamma. By inducing the overexpression of IFN-gammaR chains, NO decides whether IFN-gamma promotes cell proliferation or the induction of apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Apoptosis / immunology*
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Cell Division / drug effects
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Cell Division / immunology
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Cells, Cultured
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DNA-Binding Proteins / biosynthesis
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Dose-Response Relationship, Immunologic
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Growth Inhibitors / metabolism
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Growth Inhibitors / pharmacology
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Growth Inhibitors / physiology*
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Humans
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Interferon Regulatory Factor-1
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Interferon gamma Receptor
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Interferon-gamma / metabolism
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Interferon-gamma / pharmacology
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Interferon-gamma / physiology*
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Lymphoma, T-Cell / pathology
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Nitric Oxide / metabolism
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Nitric Oxide / pharmacology
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Nitric Oxide / physiology*
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Nitric Oxide Donors / metabolism
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Nitroprusside / pharmacology
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Nitroso Compounds / pharmacology
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Phosphoproteins / biosynthesis
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / biosynthesis
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Receptors, Interferon / biosynthesis
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Receptors, Interleukin-2 / biosynthesis
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T-Lymphocytes / cytology*
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
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Time Factors
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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Growth Inhibitors
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IRF1 protein, human
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Interferon Regulatory Factor-1
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NOC 12
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Nitric Oxide Donors
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Nitroso Compounds
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Phosphoproteins
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Proto-Oncogene Proteins c-bcl-2
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Receptors, Interferon
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Receptors, Interleukin-2
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Nitroprusside
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Nitric Oxide
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Interferon-gamma