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Our studies in the experimental human model showed for the first time that the production of IFN-gamma was decreased, whereas the production of IL-4, IL-6 and IL-10 was not affected due to zinc deficiency</csml:comment>
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IFN- gamma is the major component of the Th1 response panel, and it upregulates major histocompatibility complex class I antigen expression.</csml:comment>
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Because zinc deficiency affects IL-2 production and T-cell activation adversely, we have investigated the role of zinc on NF-KappaB (nuclear factor-kappaB) activation in HUT-78, a T helper 0 (Th0) human malignant lymphoblastoid cell line.</csml:comment>
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We showed for the first time that, in zinc deficient HUT-78 cells, the activation of NF-KappaB was affected adversely</csml:comment>
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<csml:comment type="text">PMID: 18385818
Zinc deficiency caused a 60percent decrease in phosphorylated IKappaB-alpha in non-stimulated and 40percent decrease in phorbol-12 myristate 13 acetate (PMA)/phytohemagglutinin-p (PHA-p)–stimulated cells, compared with zinc-sufficient cells

PMID: 18385818,11574819
We showed that the phosphorylation of IKappaB and IKK, translocation of NF-KappaB, and its binding to DNA in HUT-78 cells were all zinc dependent</csml:comment>
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Zinc deficiency caused a 60percent decrease in phosphorylated IKappaB-alpha in non-stimulated and 40percent decrease in phorbol-12 myristate 13 acetate (PMA)/phytohemagglutinin-p (PHA-p)–stimulated cells, compared with zinc-sufficient cells

PMID: 18385818,11574819
We showed that the phosphorylation of IKappaB and IKK, translocation of NF-KappaB, and its binding to DNA in HUT-78 cells were all zinc dependent</csml:comment>
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Zinc deficiency caused a 60percent decrease in phosphorylated IKappaB-alpha in non-stimulated and 40percent decrease in phorbol-12 myristate 13 acetate (PMA)/phytohemagglutinin-p (PHA-p)–stimulated cells, compared with zinc-sufficient cells

PMID: 18385818,11574819
We showed that the phosphorylation of IKappaB and IKK, translocation of NF-KappaB, and its binding to DNA in HUT-78 cells were all zinc dependent</csml:comment>
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Zinc deficiency decreased IKK- alpha in PMA/PHA-p–stimulated cells by 30percent in comparison to zinc-sufficient cells.

PMID: 18385818,11574819
We showed that the phosphorylation of IKappaB and IKK, translocation of NF-KappaB, and its binding to DNA in HUT-78 cells were all zinc dependent</csml:comment>
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Zinc deficiency decreased IKK- alpha in PMA/PHA-p–stimulated cells by 30percent in comparison to zinc-sufficient cells.

PMID: 18385818,11574819
We showed that the phosphorylation of IKappaB and IKK, translocation of NF-KappaB, and its binding to DNA in HUT-78 cells were all zinc dependent</csml:comment>
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Zinc deficiency caused a 50% reduction of ubiquitinated IKappaB-alpha after PMA/PHA-p stimulation
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Zinc deficiency caused a 50% reduction of ubiquitinated IKappaB-alpha after PMA/PHA-p stimulation
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We showed that the phosphorylation of IKappaB and IKK, translocation of NF-KappaB, and its binding to DNA in HUT-78 cells were all zinc dependent</csml:comment>
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We showed that the phosphorylation of IKappaB and IKK, translocation of NF-KappaB, and its binding to DNA in HUT-78 cells were all zinc dependent</csml:comment>
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We showed that the phosphorylation of IKappaB and IKK, translocation of NF-KappaB, and its binding to DNA in HUT-78 cells were all zinc dependent</csml:comment>
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The NADPH oxidases are a group of plasma membrane associated enzymes, which catalyze the production of O2.− from oxygen by using NADPH as the electron donor.

PMID: 18385818
Zinc is an inhibitor of this enzyme</csml:comment>
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Zinc is known to induce the production of metallothionein, which is very rich in cysteine, and is an excellent scavenger of .OH</csml:comment>
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<csml:comment type="text">PMID: 18385818
Iron and copper ions catalyze the production of .OH from H2O2.

PMID: 18385818
Zinc is known to compete with both iron and copper for binding to cell membrane, thus decreasing the production of .OH </csml:comment>
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A few investigators have reported that inflammatory cytokines such as TNF-alpha (tumor necrosis factor-alpha) and IL-1beta, generated by activated monocytes-macrophages, also are known to produce increased amounts of ROS</csml:comment>
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A few investigators have reported that inflammatory cytokines such as TNF-alpha (tumor necrosis factor-alpha) and IL-1beta, generated by activated monocytes-macrophages, also are known to produce increased amounts of ROS</csml:comment>
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One such inhibitor of NF-KappaB activation is A20, a zinc finger-transactivating factor which also binds to DNA, producing the A20 protein which inhibits TNF-alpha-induced NF-KappaB activation</csml:comment>
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A20 plays an important role in reducing IL-1beta- and TNF-alpha-induced NF-kappaB activation</csml:comment>
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One such inhibitor of NF-KappaB activation is A20, a zinc finger-transactivating factor which also binds to DNA, producing the A20 protein which inhibits TNF-alpha-induced NF-KappaB activation.

PMID: 18385818,15451058
In addition, we provided evidence to show that, in the human pro-myelocytic leukemia cell line HL-60 which differentiates to the monocyte-macrophage phenotype by PMA, zinc increased the expression of A20 and the binding of A20 transactivating factor to DNA, thereby enhancing inhibition of induced NF-KappaB activation</csml:comment>
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Our data showed that zinc supplementation to normal healthy subjects inhibits the induction of TNF-alpha and IL-1beta mRNA in MNCs</csml:comment>
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Our data showed that zinc supplementation to normal healthy subjects inhibits the induction of TNF-alpha and IL-1beta mRNA in MNCs</csml:comment>
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In addition, we provided evidence to show that, in the human pro-myelocytic leukemia cell line HL-60 which differentiates to the monocyte-macrophage phenotype by PMA, zinc increased the expression of A20 and the binding of A20 transactivating factor to DNA, thereby enhancing inhibition of induced NF-KappaB activation</csml:comment>
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A20 is expressed in various types of cells in response to a number of stimuli such as TNF-alpha, IL-1beta, LPS (lipopolysaccharide), PMA, Epstein-Barr virus latent membrane protein, as well as other stimuli</csml:comment>
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A20 is expressed in various types of cells in response to a number of stimuli such as TNF-alpha, IL-1beta, LPS (lipopolysaccharide), PMA, Epstein-Barr virus latent membrane protein, as well as other stimuli</csml:comment>
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In addition, we provided evidence to show that, in the human pro-myelocytic leukemia cell line HL-60 which differentiates to the monocyte-macrophage phenotype by PMA, zinc increased the expression of A20 and the binding of A20 transactivating factor to DNA, thereby enhancing inhibition of induced NF-KappaB activation</csml:comment>
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In addition, we provided evidence to show that, in the human pro-myelocytic leukemia cell line HL-60 which differentiates to the monocyte-macrophage phenotype by PMA, zinc increased the expression of A20 and the binding of A20 transactivating factor to DNA, thereby enhancing inhibition of induced NF-KappaB activation</csml:comment>
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Thymulin binds to high-affinity receptors on T cells, induces several T-cell markers, and promotes T-cell function, including allogenic cytotoxicity, suppressor functions, and interleukin-2 (IL-2) production.</csml:comment>
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Thymulin binds to high-affinity receptors on T cells, induces several T-cell markers, and promotes T-cell function, including allogenic cytotoxicity, suppressor functions, and interleukin-2 (IL-2) production.</csml:comment>
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Thymulin binds to high-affinity receptors on T cells, induces several T-cell markers, and promotes T-cell function, including allogenic cytotoxicity, suppressor functions, and interleukin-2 (IL-2) production.</csml:comment>
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The dismutation of O2.−to H2O2 is catalyzed by an enzyme super oxide dismutase (SOD), which contains both copper and zinc. </csml:comment>
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IL-2 also is involved in the differentiation of thymocytes, peripheral T- and B-lymphocytes and other cells of hematopoietic origin
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IL-2 also is involved in the differentiation of thymocytes, peripheral T- and B-lymphocytes and other cells of hematopoietic origin
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IL-2 also is involved in the differentiation of thymocytes, peripheral T- and B-lymphocytes and other cells of hematopoietic origin
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Following PMA/PHA-p stimulation, the IL-2 production and IL-2 mRNA were significantly greater in zinc-sufficient cells in comparison to the zinc-deficient cells</csml:comment>
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Following PMA/PHA-p stimulation, the IL-2 production and IL-2 mRNA were significantly greater in zinc-sufficient cells in comparison to the zinc-deficient cells</csml:comment>
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Similar results were seen for soluble IL-2 receptor alpha (soluble IL-2Ralpha) production and gene expression
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Induction of IL-2Ralphagene expression also is mediated by the induced nuclear expression of NF-KappaB</csml:comment>
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