The hexosamine biosynthesis pathway negatively regulates IL-2 production by Jurkat T cells.
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.
Huang
Ji-Biao
JB
Department of Ophthalmology and Visual Sciences, The University of Michigan Medical School, 1000 Wall Street, Ann Arbor, MI 48105, USA.
Clark
Andrea J
AJ
Petty
Howard R
HR
D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005944:Glucosamine / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006595:Hexosamines / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D006595:Hexosamines; D007376:Interleukin-2; D005947:Glucose; D005944:Glucosamine