Zinc chelation decreases IFN-β-induced STAT1 upregulation and iNOS expression in RAW 264.7 macrophages.

One consequence of lipopolysaccharide (LPS)-induced stimulation of macrophages is the release of Interferon (IFN)-β, and subsequently the activation of the JAK-STAT1 pathway, resulting in the expression of inducible nitric oxide synthase (iNOS). Free intracellular zinc ions (Zn) have a profound impact as a second messenger in LPS-dependent gene expression. Previous work had indicated a Zn-dependent upregulation of STAT1 mRNA in response to LPS and IFN-β, potentially affecting STAT1-dependent downstream signaling upon pre-incubation with these agents.

Ethylmercury and Hg2+ induce the formation of neutrophil extracellular traps (NETs) by human neutrophil granulocytes.

Humans are exposed to different mercurial compounds from various sources, most frequently from dental fillings, preservatives in vaccines, or consumption of fish. Among other toxic effects, these substances interact with the immune system. In high doses, mercurials are immunosuppressive.

PTEN-inhibition by zinc ions augments interleukin-2-mediated Akt phosphorylation.

Free zinc ions (Zn(2+)) participate in several signaling pathways. The aim of the present study was to investigate a potential involvement of Zn(2+) in the PI3K/Akt pathway of interleukin (IL)-2 signaling in T-cells. The IL-2 receptor triggers three major pathways, ERK1/2, JAK/STAT5, and PI3K/Akt.

Application of Zinpyr-1 for the investigation of zinc signals in Escherichia coli.

Changes of the pico- to nanomolar concentration of free intracellular Zn(2+) are part of the signal transduction in mammalian cells. These zinc signals regulate the enzymatic activity of target proteins such as protein tyrosine phosphatases. For Escherichia coli, previous studies have reported diverging concentrations from femto- to picomolar, raising the question if Zn(2+) could also have a function in bacterial signaling.

Mercuric ions inhibit mitogen-activated protein kinase dephosphorylation by inducing reactive oxygen species.

Mercury intoxication profoundly affects the immune system, in particular, signal transduction of immune cells. However, the mechanism of the interaction of mercury with cellular signaling pathways, such as mitogen activated protein kinases (MAPK), remains elusive. Therefore, the objective of this study is to investigate three potential ways in which Hg(2+) ions could inhibit MAPK dephosphorylation in the human T-cell line Jurkat: (1) by direct binding to phosphatases; (2) by releasing cellular zinc (Zn(2+)); and (3) by inducing reactive oxygen species (ROS).

Cadmium ions promote monocytic differentiation of human leukemia HL-60 cells treated with 1α,25-dihydroxyvitamin D3.

Cadmium exposure has multiple effects on the immune system. These can be stimulating, leading to improved clearance of infections, or inhibiting, increasing susceptibility toward infectious agents. One in vivo observation in cadmium-exposed individuals is increased monocyte numbers.

Cadmium ions induce monocytic production of tumor necrosis factor-alpha by inhibiting mitogen activated protein kinase dephosphorylation.

Cadmium ions (Cd(2+)) are carcinogenic and have cytotoxic effects in a variety of organisms. In addition to its direct cytotoxicity, Cd(2+) acts as an immunomodulator at sub-toxic concentrations. Among other influences Cd(2+) can induce inflammation, but the molecular basis for this effect is not well investigated.

Effects of long-term zinc supplementation and deprivation on gene expression in human THP-1 mononuclear cells.

Zinc is an essential trace element that is critical for cellular function and structural integrity. It has an important regulatory role in the immune system, in particular in monocytes. To identify the diverse cellular targets and mechanisms of action of zinc in this cell type, we used microarray technology to assess the effects of zinc supplementation and depletion on global gene expression.

Zinc ions cause the thimerosal-induced signal of fluorescent calcium probes in lymphocytes.

Most fluorescent probes for the investigation of calcium signaling also detect zinc ions. Consequently, changes in the intracellular zinc concentration could be mistaken for calcium signals. Thimerosal (TMS) is used as a calcium-mobilizing agent and we analyzed the contribution of zinc ions to the signal observed with fluorescent calcium probes after TMS stimulation.

Zinc signals are essential for lipopolysaccharide-induced signal transduction in monocytes.

Cytosolic alterations of calcium ion concentrations are an integral part of signal transduction. Similar functions have been hypothesized for other metal ions, in particular zinc (Zn(2+)), but this still awaits experimental verification. Zn(2+) is important for multiple cellular functions, especially in the immune system.

Zinc-dependent suppression of TNF-alpha production is mediated by protein kinase A-induced inhibition of Raf-1, I kappa B kinase beta, and NF-kappa B.

Excessive and permanent cytokine production in response to bacterial LPS causes cell and tissue damage, and hence organ failure during sepsis. We have previously demonstrated that zinc treatment prevents LPS-induced TNF-alpha expression and production in human monocytes by inhibiting cyclic nucleotide phosphodiesterase (PDE) activity and expression, and subsequent elevation of the cyclic nucleotide cGMP. In the present study, we investigated the molecular mechanism by which cGMP signaling affects the LPS-induced signaling cascade to suppress TNF-alpha transcription and release from monocytes.

Differential gene expression after zinc supplementation and deprivation in human leukocyte subsets.

An individual's zinc status has a significant impact on the immune system, and zinc deficiency, as well as supplementation, modulates immune function. To investigate the effects of zinc on different leukocyte subsets, we used microarray technology to analyze and compare the changes in mRNA expression in cell culture models of monocytes (THP-1), T cells (Jurkat), and B cells (Raji), in response to supplementation for 40 h with 50 microM zinc or 2.5 microM of the membrane-permeant zinc chelator TPEN [N,N,N',N'-tetrakis-(2-pyridyl-methyl)ethylenediamine], respectively.

Flow cytometric measurement of labile zinc in peripheral blood mononuclear cells.

Labile (i.e., free or loosely bound) zinc has the potential to modulate cellular function.