Copper deficiency reduces interleukin-2 (IL-2) production and IL-2 mRNA in human T-lymphocytes.
Although dietary copper (Cu) deficiency has been associated with decreased production of interleukin-2 (IL-2) by activated splenic mononuclear cells in rodent models, the basis for this relationship and its relevance for humans remain unknown. To address these matters, we have developed an in vitro model of cellular copper deficiency by treating Jurkat, a human T-lymphocyte cell line, with low concentrations of 2,3,2-tetraamine (2,3,2-tet), a high affinity copper chelator. Exposure to 5-20 micromol/L 2,3,2-tet for 35 h decreased cell copper and the activity of Cu,Zn-superoxide dismutase (Cu,Zn-SOD) by 30-40% and IL-2 production by 60-70% in cultures activated with phytohemagglutinin and phorbol myristate acetate. Similarly, IL-2 mRNA levels were 40-70% lower in chelator-treated cells than in untreated cells at 3-12 h after activation. In contrast, chelator treatment had no significant effect on cell viability, growth, protein synthesis or mitochondrial activity. The presence of a slight molar excess of copper, but not zinc or iron, during exposure to 2,3,2-tet prevented the chelator-induced decrease in Cu,Zn-SOD activity and the reductions in IL-2 mRNA and bioactivity. Moreover, binding of diferric transferrin (Tf) and cellular uptake of Tf-59Fe by Jurkat cells were not increased by 2,3,2-tet, indicating that chelator-treated cells were not iron deficient. Finally, incubation of human peripheral blood mononuclear cells (PBMC) with 2,3,2-tet decreased mitogen-induced IL-2 production by 50% compared with untreated controls. These data indicate that a decline in copper status decreases IL-2 production by activated human T-cells due to reduced synthesis and/or stability of IL-2 mRNA.
Hopkins
R G
RG
Department of Food, Nutrition & Food Service Management, The University of North Carolina Greensboro, 27412-5001, USA.
Failla
M L
ML
D015152:Blotting, Northern; D003300:Copper / Q000172:deficiency*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D013482:Superoxide Dismutase / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D003300:Copper; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate