An approach has been optimized permitting measurement of human cytokine reporter gene expression after transient transfection directly into purified human peripheral blood T lymphocytes. Comparing the expression of interleukin 2 (IL-2) CAT with a series of specially engineered gamma interferon (IFN-gamma) constructs, a fundamental difference in the molecular mechanisms regulating these two cytokines has been suggested. A potent, tissue-specific, constitutive-acting positive regulatory element was located between sequences -215 and -53 in the human IFN-gamma gene. Deletion analyses suggested that sequences slightly upstream, between positions -251 to -215, exerted a powerful dominant suppressive influence over that positive element. Negative elements appear to play a major role in controlling the regulation of human IFN-gamma gene expression. We thus propose a model of cytokine gene regulation in which selective derepression may be an important fundamental mechanism of induction and/or positive modulation.
Article|
August 01 1990
A model of human cytokine regulation based on transfection of gamma interferon gene fragments directly into isolated peripheral blood T lymphocytes.
J C Chrivia,
J C Chrivia
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
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T Wedrychowicz,
T Wedrychowicz
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
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H A Young,
H A Young
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
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K J Hardy
K J Hardy
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
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J C Chrivia
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
T Wedrychowicz
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
H A Young
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
K J Hardy
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1990) 172 (2): 661–664.
Citation
J C Chrivia, T Wedrychowicz, H A Young, K J Hardy; A model of human cytokine regulation based on transfection of gamma interferon gene fragments directly into isolated peripheral blood T lymphocytes.. J Exp Med 1 August 1990; 172 (2): 661–664. doi: https://doi.org/10.1084/jem.172.2.661
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