Interleukin-7 mediates glucose utilization in lymphocytes through transcriptional regulation of the hexokinase II gene

    Authors

    M. Chehtane;A. R. Khaled

    Comments

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    Abbreviated Journal Title

    Am. J. Physiol.-Cell Physiol.

    Keywords

    cytokine; metabolism; signaling; ATP; RECEPTOR-DEFICIENT MICE; ACUTE LYMPHOBLASTIC-LEUKEMIA; NAIVE T-CELLS; SIGNAL-TRANSDUCTION; INTRACELLULAR ATP; GAMMA-CHAIN; AEROBIC GLYCOLYSIS; TRANSPORTER GLUT1; CYTOKINE; SURVIVAL; Cell Biology; Physiology

    Abstract

    Chehtane M, Khaled AR. Interleukin-7 mediates glucose utilization in lymphocytes through transcriptional regulation of the hexokinase II gene. Am J Physiol Cell Physiol 298: C1560-C1571, 2010. First published March 3, 2010; doi:10.1152/ajpcell.00506.2009.-The cytokine interleukin-7 (IL-7) has essential growth activities that maintain the homeostatic balance of the immune system. Little is known of the mechanism by which IL-7 signaling regulates metabolic activity in support of its vital function in lymphocytes. We observed that IL-7 deprivation caused a rapid decline in the metabolism of glucose that was attributable to loss of intracellular glucose retention. To identify the transducer of the IL-7 metabolic signal, we examined the expression of three important regulators of glucose metabolism, the glucose transporter GLUT-1 and two glycolytic enzymes, hexokinase II (HXKII) and phosphofructokinase-1 (PFK-1), using an IL-7dependent T-cell line and primary lymphocytes. We found that in lymphocytes deprived of IL-7 loss of glucose uptake correlated with decreased expression of HXKII. Readdition of IL-7 to cytokine-deprived lymphocytes restored the transcription of the HXKII gene within 2 h, but not that of GLUT-1 or PFK-1. IL-7-mediated increases in HXKII, but not GLUT-1 or PFK-1, were also observed at the protein level. Inhibition of HXKII with 3-bromopyruvate or specific small-interfering RNA decreased glucose utilization, as well as ATP levels, in the presence of IL-7, whereas overexpression of HXKII, but not GLUT-1, restored glucose retention and increased ATP levels in the absence of IL-7. We conclude that IL-7 controls glucose utilization by regulating the gene expression of HXKII, suggesting a mechanism by which IL-7 supports bioenergetics that control cell fate decisions in lymphocytes.

    Journal Title

    American Journal of Physiology-Cell Physiology

    Volume

    298

    Issue/Number

    6

    Publication Date

    1-1-2010

    Document Type

    Article

    Language

    English

    First Page

    C1560

    Last Page

    C1571

    WOS Identifier

    WOS:000277949300032

    ISSN

    0363-6143

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