Zinc at pharmacologic concentrations affects cytokine expression and induces apoptosis of human peripheral blood mononuclear cells

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2006-05, Vol.22 (5), p.465-474
• Main Authors: Chang, Kee-Lung, Hung, Thu-Ching, Hsieh, Bau-Shan, Chen, Yen-Hui, Chen, Te-Fu, Cheng, Hsiao-Ling
• Format: Article
• Language: English
• Subjects: Adult; antiapoptosis; Apoptosis; Apoptosis - drug effects; Base Sequence; bcl-X Protein - drug effects; bcl-X Protein - metabolism; Biological and medical sciences; Blood; Blotting, Western; c-fos; Caspase 3; Caspases - metabolism; Cell adhesion & migration; Cell culture; Cell cycle; Cell Cycle - drug effects; Cells, Cultured; Cytokines - drug effects; Cytokines - metabolism; Cytokines, Apoptosis; Deoxyribonucleic acid; DNA; DNA Fragmentation; Dose-Response Relationship, Drug; Fas Ligand Protein; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Genes, bcl-2 - drug effects; Genes, fos - drug effects; Humans; Immune response; Immune system; immunocompetence; immunostimulants; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - immunology; lymphocytes; lymphokines; Male; Membrane Glycoproteins - drug effects; Membrane Glycoproteins - metabolism; Mitochondria; NF-kappa B - drug effects; NF-kappa B - metabolism; Nuclear factor-κB; nutrient deficiencies; peripheral nervous system; pharmacology; Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA - metabolism; sigma factors; Studies; Trace Elements - pharmacology; Tumor Necrosis Factors - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Zinc; Zinc - pharmacology
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/j.nut.2005.11.009

The present study examined the effect of zinc at concentrations of the apoptotic signaling pathway and immune function of peripheral blood mononuclear cells (PBMCs). PBMCs from healthy subjects were treated in vitro with various zinc concentrations to imitate different serum statuses of physiologic (2 to 15 μM) and pharmacologic (15 to 100 μM) concentrations to higher than 100 μM and analyzed their expressions of cytokines and apoptotically related factors. Although a normal physiologic concentration of zinc had no effect on immunologic function or apoptosis of PBMCs, a pharmacologic concentration (100 μM) or higher affected both functions. Zinc decreased cell proliferation at concentrations higher than 100 μM and stimulated cytokine expression at concentrations of at least 100 μM. Further, at concentrations of at least 100 μM, apoptosis was induced, and expressions of caspase-3 and proapoptotic genes, including Fas (FasL) and c-fos, which trigger apoptosis through receptor-mediated extrinsic and mitochondrion-mediated apoptotic pathways, respectively, were increased. At concentrations at least 300 μM, expressions of antiapoptotic factors nuclear factor-κB, Bcl-2, and Bcl-X L were markedly decreased. Zinc stimulates cytokine expression and induces apoptosis of PBMCs from healthy subjects only at concentrations equal to or greater than the serum pharmacologic range. Receptor-mediated extrinsic and mitochondrial-mediated intrinsic pathways are involved in this zinc-induced apoptosis.