ArticlePloS one2017
Zinc Modulates Endotoxin-Induced Human Macrophage Inflammation through ZIP8 Induction and C/EBPβ Inhibition.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Article
- Overlaps in mammalian iron and manganese homeostasis: recent advances.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- The role of metal ions iron, copper, and zinc in the immune microenvironment of gastric cancer.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Unveiling the prognostic and therapeutic landscape of the zinc transporter protein SLC39A family in colorectal cancer through multi-omics and machine learning approaches.Clinical and experimental medicine · 2026Article
- Zinc: a metallic shield against cardiac inflammation.Metallomics : integrated biometal science · 2026Review
- ZIP8 loss impairs macrophage-mediated phagolysosomal removal of bacteria and is overcome by butyrate supplementation.Communications biology · 2026Article
- Impact of bovine respiratory disease on tissue-specific regulation of Zn and vitamin a metabolism and apparent absorption and retention of trace minerals.Journal of animal science · 2026Article
- Serum zinc dynamics as a diagnostic and immunomodulatory biomarker in neonatal sepsis.Scientific reports · 2025Article
- Mechanism and regulatory strategy study on promoting vascularized bone regeneration via intracellular zinc ion transport.Bioactive materials · 2025Article
- VEGF in Diabetic Retinopathy and Age-Related Macular Degeneration.International journal of molecular sciences · 2025Review
- Human genetic variants in SLC39A8 impact uptake and steady-state metal levels within the cell.Life science alliance · 2025Article
- SLC30 (ZnT) and SLC39 (ZIP) zinc transporter families: from gatekeepers of zinc homeostasis to promoters of tumorigenesis and targets for clinical therapy.Frontiers in immunology · 2025Review
- Sequence variants associated with resilient responses in growing pigs.Journal of animal breeding and genetics = Zeitschrift fur Tierzuchtung und Zuchtungsbiologie · 2025Article
- A key protein fromIBRO neuroscience reports · 2023Article
- Trace metal elements: a bridge between host and intestinal microorganisms.Science China. Life sciences · 2023Review
- Iron Chelation as a Potential Therapeutic Approach in Acute Lung Injury.Life (Basel, Switzerland) · 2023Review
- The Inherited Intestinal Microbiota from Myeloid-Specific ZIP8KO Mice Impairs Pulmonary Host Defense against Pneumococcal Pneumonia.Pathogens (Basel, Switzerland) · 2023Article
- Novel strategies for cancer immunotherapy: counter-immunoediting therapy.Journal of hematology & oncology · 2023Review
- A mouse model characterizes the roles of ZIP8 in systemic iron recycling and lung inflammation and infection.Blood advances · 2023Article
- Soluble Carrier Transporters and Mitochondria in the Immunometabolic Regulation of Macrophages.Antioxidants & redox signaling · 2022Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Two vital functions of the innate immune system are to initiate inflammation and redistribute micronutrients in favor of the host. Zinc is an essential micronutrient used in host defense. The zinc importer ZIP8 is uniquely induced through stimulation of the NF-κB pathway by LPS in monocytes and functions to regulate inflammation in a zinc-dependent manner. Herein we determined the impact of zinc metabolism following LPS-induced inflammation in human macrophages. We observed that ZIP8 is constitutively expressed in resting macrophages and strikingly elevated following LPS exposure, a response that is unique compared to the 13 other known zinc import proteins. During LPS exposure, extracellular zinc concentrations within the physiological range markedly reduced IL-10 mRNA expression and protein release but increased mRNA expression of TNFα, IL-8, and IL-6. ZIP8 knockdown inhibited LPS-driven cellular accumulation of zinc and prevented zinc-dependent reduction of IL-10 release. Further, zinc supplementation reduced nuclear localization and activity of C/EBPβ, a transcription factor known to drive IL-10 expression. These studies demonstrate for the first time that zinc regulates LPS-mediated immune activation of human macrophages in a ZIP8-dependent manner, reducing IL-10. Based on these findings we predict that macrophage zinc metabolism is important in host defense against pathogens.
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