Abstract
Zinc is a trace element that is essential for the function of many enzymes and transcription factors. Zinc deficiency results in defects in innate and acquired immune responses. However, little is known about the mechanism(s) by which zinc affects immune cell function. Here we show that stimulation with the Toll-like receptor 4 agonist lipopolysaccharide (LPS) altered the expression of zinc transporters in dendritic cells and thereby decreased intracellular free zinc. A zinc chelator mimicked the effects of LPS, whereas zinc supplementation or overexpression of the gene encoding Zip6, a zinc transporter whose expression was reduced by LPS, inhibited LPS-induced upregulation of major histocompatibility complex class II and costimulatory molecules. These results establish a link between Toll-like receptor signaling and zinc homeostasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cation Transport Proteins / genetics*
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Cell Differentiation
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Chelating Agents / pharmacology
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Dendritic Cells / chemistry
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Dendritic Cells / cytology
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Dendritic Cells / drug effects
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Dendritic Cells / immunology*
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Gene Expression / drug effects
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Histocompatibility Antigens Class II / analysis
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Histocompatibility Antigens Class II / metabolism
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Homeostasis
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Lipopolysaccharides / pharmacology
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Lysosomal-Associated Membrane Protein 2 / analysis
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Lysosomal-Associated Membrane Protein 2 / metabolism
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Mice
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Signal Transduction
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Toll-Like Receptor 4 / agonists
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Toll-Like Receptor 4 / metabolism*
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Transcriptional Activation
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Up-Regulation
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Zinc / deficiency
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Zinc / metabolism*
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Zinc / pharmacology
Substances
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Cation Transport Proteins
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Chelating Agents
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Histocompatibility Antigens Class II
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Lipopolysaccharides
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Lysosomal-Associated Membrane Protein 2
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Tlr4 protein, mouse
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Toll-Like Receptor 4
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Zinc