ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Natural forms of vitamin E and 13'-carboxychromanol, a long-chain vitamin E metabolite, inhibit leukotriene generation from stimulated neutrophils by blocking calcium influx and suppressing 5-lipoxygenase activity, respectively.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
44 citing papers in PubMed, 88 citations in OpenAlex.
- Vitamin E, γ-tocopherol, reduces airway neutrophil recruitment after inhaled endotoxin challenge in rats and in healthy volunteers.Free radical biology & medicine · 2013Trial
- The effects of different forms of vitamin E on gut microbiota, mechanisms, and implications in disease prevention.The Journal of nutritional biochemistry · 2026Review
- α-Tocopherol and γ-tocopherol decrease inflammatory response and insulin resistance during the interaction of adipocytes and macrophages.Nutrition research and practice · 2024Article
- The Role of Vitamin E Isoforms and Metabolites in Cancer Prevention: Mechanistic Insights into Sphingolipid Metabolism Modulation.Nutrients · 2024Review
- Differential intestinal microbes and metabolites between Behcet's uveitis and Fuchs syndrome.Heliyon · 2024Article
- Antioxidant and Anti-Tumor Effects of Dietary Vitamins A, C, and E.Antioxidants (Basel, Switzerland) · 2023Review
- Effects of Histamine and the α-Tocopherol Metabolite α-13'-COOH in an Atopic Dermatitis Full-Thickness Skin Model.Molecules (Basel, Switzerland) · 2023Article
- Different forms of vitamin E and metabolite 13'-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13'-carboxychromanols are competitive inhibitors of 5-lipoxygenase.The Journal of nutritional biochemistry · 2022Article
- Metabolism of natural forms of vitamin E and biological actions of vitamin E metabolites.Free radical biology & medicine · 2022Article
- Gamma-tocopherol, a major form of vitamin E in diets: Insights into antioxidant and anti-inflammatory effects, mechanisms, and roles in disease management.Free radical biology & medicine · 2022Article
- Exploration of Long-Chain Vitamin E Metabolites for the Discovery of a Highly Potent, Orally Effective, and Metabolically Stable 5-LOX Inhibitor that Limits Inflammation.Journal of medicinal chemistry · 2021Article
- Vitamin E beyond Its Antioxidant Label.Antioxidants (Basel, Switzerland) · 2021Review
- Inflammation Drives Alzheimer's Disease: Emphasis on 5-lipoxygenase Pathways.Current neuropharmacology · 2021Review
- Appraising the role of circulating concentrations of micro-nutrients in epithelial ovarian cancer risk: A Mendelian randomization analysis.Scientific reports · 2020Article
- Tocopherols and Tocotrienols Are Bioavailable in Rats and Primarily Excreted in Feces as the Intact Forms and 13'-Carboxychromanol Metabolites.The Journal of nutrition · 2020Article
- Diversity of Chromanol and Chromenol Structures and Functions: An Emerging Class of Anti-Inflammatory and Anti-Carcinogenic Agents.Frontiers in pharmacology · 2020Review
- Omega 3-DHA and Delta-Tocotrienol Modulate Lipid Droplet Biogenesis and Lipophagy in Breast Cancer Cells: the Impact in Cancer Aggressiveness.Nutrients · 2019Article
- The Role of Tocotrienol in Protecting Against Metabolic Diseases.Molecules (Basel, Switzerland) · 2019Review
- The Effectiveness of Vitamin E Treatment in Alzheimer's Disease.International journal of molecular sciences · 2019Review
- Endogenous metabolites of vitamin E limit inflammation by targeting 5-lipoxygenase.Nature communications · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Leukotrienes generated by 5-lipoxygenase (5-LOX)-catalyzed reaction are key regulators of inflammation. In ionophore-stimulated (A23187; 1-2.5 μM) human blood neutrophils or differentiated HL-60 cells, vitamin E forms differentially inhibited leukotriene B(4) (LTB(4)) with an IC(50) of 5-20 μM for γ-tocopherol, δ-tocopherol (δT), and γ-tocotrienol, but a much higher IC(50) for α-tocopherol. 13'-Carboxychromanol, a long-chain metabolite of δT, suppressed neutrophil- and HL-60 cell-generated LTB(4) with an IC(50) of 4-7 μM and potently inhibited human recombinant 5-LOX activity with an IC(50) of 0.5-1 μM. In contrast, vitamin E forms had no effect on human 5-LOX activity but impaired ionophore-induced intracellular calcium increase and calcium influx as well as the subsequent signaling including ERK1/2 phosphorylation and 5-LOX translocation from cytosol to the nucleus, a key event for 5-LOX activation. Further investigation showed that δT suppressed cytosolic Ca(2+) increase and/or LTB(4) formation triggered by ionophores, sphingosine 1-phosphate, and lysophosphatidic acid but not by fMLP or thapsigargin, whereas 13'-carboxychromanol decreased cellular production of LTB(4) regardless of different stimuli, consistent with its strong inhibition of the 5-LOX activity. These observations suggest that δT does not likely affect fMLP receptor-mediated signaling or store depletion-induced calcium entry. Instead, we found that δT prevented ionophore-caused cytoplasmic membrane disruption, which may account for its blocking of calcium influx. These activities by vitamin E forms and long-chain carboxychromanol provide potential molecular bases for the differential anti-inflammatory effects of vitamin E forms in vivo.
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Registered trials
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.