ArticleAmerican journal of physiology. Lung cellular and molecular physiology2010
Zinc modulates the innate immune response in vivo to polymicrobial sepsis through regulation of NF-kappaB.
Article in American journal of physiology. Lung cellular and molecular physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 142 citations in OpenAlex.
- Zinc Supplementation, Inflammation, and Gut Integrity Markers in HIV Infection: A Randomized Placebo-Controlled Trial.Nutrients · 2025Trial
- Observational
- Zinc Signaling in Acute Kidney Injury.Cells · 2026Review
- Low zinc status and long-term risk of incident sepsis in patients with type 2 diabetes: a multicenter cohort study.Frontiers in nutrition · 2026Article
- Exercise decreases the number and modifies the transcriptome of M1 macrophages and CD8American journal of physiology. Cell physiology · 2025Article
- Targeting alveolar macrophages: a promising intervention for pulmonary infection and acute lung injury.Cellular & molecular biology letters · 2025Review
- The intracellular domain of TLR2 is capable of high-affinity Zn binding: possible outcomes for the receptor activation.FEBS letters · 2025Article
- Hepatic zinc deficiency dampens the acute phase response in patients with alcohol-associated hepatitis.Frontiers in immunology · 2025Article
- Impaired ATP hydrolysis in blood plasma contributes to age-related neutrophil dysfunction.Immunity & ageing : I & A · 2024Article
- The Role of Zinc in Developed Countries in Pediatric Patients: A 360-Degree View.Biomolecules · 2024Review
- Regulation of anti-tumor immunity by metal ion in the tumor microenvironment.Frontiers in immunology · 2024Review
- Evaluation of Micronutrients and Pro-Inflammatory Cytokines Levels in Nutritionally Deprived Children-A Tertiary Care Hospital-Based Study.Nutrients · 2023Article
- Human protozoa infection and dysplasia in ulcerative colitis: a neglected aspect in a prominent disease.Parasitology research · 2023Article
- The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in COVID-19 and Sepsis.Antioxidants (Basel, Switzerland) · 2023Review
- Zinc deficiency impairs axonal regeneration and functional recovery after spinal cord injury by modulating macrophage polarization via NF-κB pathway.Frontiers in immunology · 2023Article
- Tumor cell cytoplasmic metallothionein expression associates with differential tumor immunogenicity and prognostic outcome in high-grade serous ovarian carcinoma.Frontiers in oncology · 2023Article
- Piperlongumin Improves Survival in the Mouse Model of Sepsis: Effect on Coagulation Factors and Lung Inflammation.Inflammation · 2022Article
- Zinc and Respiratory Viral Infections: Important Trace Element in Anti-viral Response and Immune Regulation.Biological trace element research · 2022Review
- Zinc deficiency as a possible risk factor for increased susceptibility and severe progression of Corona Virus Disease 19.The British journal of nutrition · 2022Review
- Divalent Metal Uptake and the Role of ZIP8 in Host Defense Against Pathogens.Frontiers in cell and developmental biology · 2022Review
23 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Zinc is an essential element that facilitates coordination of immune activation during the host response to infection. We recently reported that zinc deficiency increases systemic inflammation, vital organ damage, and mortality in a small animal model of sepsis. To investigate potential mechanisms that cause these phenomena, we used the same animal model and observed that zinc deficiency increases bacterial burden and enhances NF-kappaB activity in vital organs including the lung. We conducted further studies in the lung to determine the overall impact of zinc deficiency. At the molecular level, NF-kappaB p65 DNA-binding activity was enhanced by zinc deficiency in response to polymicrobial sepsis. Furthermore, expression of the NF-kappaB-targeted genes IL-1beta, TNFalpha, ICAM-1, and the acute phase response gene SAA1/2 were elevated by zinc deficiency. Unexpectedly, the amount of NF-kappaB p65 mRNA and protein was increased in the lung including alveolar epithelia of zinc-deficient mice. These events occurred with a significant and concomitant increase in caspase-3 activity within 24 h of sepsis onset in zinc-deficient mice relative to control group. Short-term zinc supplementation reversed these effects. Reconstitution of zinc deficiency in lung epithelial cultures resulted in similar findings in response to TNFalpha. Taken together, zinc deficiency systemically enhances the spread of infection and NF-kappaB activation in vivo in response to polymicrobial sepsis, leading to enhanced inflammation, lung injury, and, as reported previously, mortality. Zinc supplementation immediately before initiation of sepsis reversed these effects thereby supporting the plausibility of future studies that explore zinc supplementation strategies to prevent sepsis-mediated morbidity and mortality.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.