Zinc enhances the expression of interleukin-2 and interleukin-2 receptors in HUT-78 cells by way of NF-kappaB activation.
Production of interleukin (IL)-2 is decreased in zinc-deficient human beings, and zinc is essential to IL-2-mediated T-cell activation. We used a human Th(0) malignant lymphoblastoid cell line, HUT-78, to study the effect of zinc on IL-2 production in PHA/PMA activated T-cells. In zinc-deficient cells, the gene expression of IL-2 was decreased by 50% compared with that in zinc-sufficient cells. The effect of zinc was specific and at the transcriptional level. We also showed a significant effect of zinc on the gene expression of IL-2 receptors alpha and beta. Binding of NF-kappaB (a zinc-dependent transcription factor) to DNA was decreased in zinc-deficient cells. Using transfection of expression vectors of anti-sense NF-kappaB p105 (precursor of NF-kappaB p50) in cells, we showed that a decrease in gene expression of IL-2 and IL-2 Ralpha may be partly due to decreased activation of NF-kappaB in zinc-deficient cells. Our studies demonstrate, for the first time, the role of zinc in gene expression of IL-2 and its receptors in HUT-78 cells. We also document that the binding of NF-kappaB to DNA was adversely affected, thereby decreasing the gene expression of IL-2 and IL-2 Ralpha in zinc-deficient HUT-78 cells.
Prasad
Ananda S
AS
Department of Medicine, Division of Hematology-Oncology, Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, University Health Center 5-C, 4201 St. Antoine, Detroit, MI 48201, USA. prasada@karmanos.org
Bao
Bin
B
Beck
Frances W J
FW
Sarkar
Fazlul H
FH
D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D015847:Interleukin-4 / Q000096:biosynthesis; D008670:Metals / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011033:Podophyllin / Q000031:analogs & derivatives* / Q000378:metabolism; D011034:Podophyllotoxin / Q000031:analogs & derivatives; D016372:RNA, Antisense / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014162:Transfection; D015032:Zinc / Q000172:deficiency / Q000494:pharmacology*
D007376:Interleukin-2; D008670:Metals; D016328:NF-kappa B; D016372:RNA, Antisense; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D018808:Transcription Factor AP-1; D015847:Interleukin-4; C003170:mitopodozide; D011033:Podophyllin; D004247:DNA; D015032:Zinc; D011034:Podophyllotoxin