The hexosamine biosynthesis pathway negatively regulates IL-2 production by Jurkat T cells
Ji-Biao Huang1, Andrea J Clark, Howard R Petty
1Department of Ophthalmology and Visual Sciences, The University of Michigan Medical School, 1000 Wall Street, Ann Arbor, MI 48105, USA.
Abstract:
To test the hypothesis that the hexosamine biosynthesis pathway (HBP) affects cytokine production, we studied IL-2 production by Jurkat cells in response to PHA. We found that the HBP activator glucosamine (GlcN), but not glucose (Glc), dose-dependently reduced IL-2 production. Importantly, GlcN blocked trafficking of a GFP-NFAT chimeric protein to the nucleus of stimulated transfectants. Not surprisingly, changes in O-GlcNAc protein modifications were noted during cell activation with and without GlcN addition. These findings could not be explained by some non-specific change in cell metabolism because ATP concentrations did not significantly change. We speculate that HBP-active compounds may contribute to patient care in certain inflammatory and autoimmune diseases.
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