Expanding extracellular zinc beyond levels reflecting the albumin-bound plasma zinc pool potentiates the capability of IL-1beta, IL-18, and IL-12 to Act as IFN-gamma-inducing factors on PBMC

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
Marco A PoleganovH Mühl

Abstract

The mixed cell population of freshly isolated peripheral blood mononuclear cells (PBMCs) is a widely used cell culture model for studying human cytokine networks, in particular production of immunoregulatory interferon-gamma (IFN-gamma). Here, we demonstrate that nontoxic concentrations of zinc (15 muM), employed as zinc chloride (ZnCl(2)), that are about 2-fold of the readily accessible pool of albumin-bound zinc in the plasma, strongly enhance the potential of interleukin-1beta (IL-1beta) to act as an IFN-gamma-inducing factor on PBMCs. In contrast, zinc supplementation approximately resembling the albumin-bound plasma pool (7.5 muM) did not significantly affect cytokine-induced IFN-gamma secretion. ZnCl(2) also amplified IFN-gamma production under the influence of IL-12 or IL-18, whereas IL-1beta-induced IL-8 expression was not enhanced by the addition of ZnCl(2), indicating that the effect observed on cytokine-induced IFN-gamma is not of a general and unspecific nature. The current observation not only agrees with the immunoregulatory aspects of zinc as seen in vivo but also indicates that modulating the extracellular pool of accessible zinc may dramatically affect cytokine biology, as observed in experimental cell research.

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Citations

Jun 15, 2011·The Journal of Clinical Investigation·Emmanuel NivetFrançois S Roman
Mar 16, 2011·Cardiology Research and Practice·S Van LinthoutC Tschöpe
Aug 12, 2016·Metallomics : Integrated Biometal Science·Francis AlbaredeToshiyuki Fujii
Jan 14, 2012·Journal of the American Chemical Society·Jin LuClaudia A Blindauer

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