ArticleProceedings of the National Academy of Sciences of the United States of America2022
sEH-derived metabolites of linoleic acid drive pathologic inflammation while impairing key innate immune cell function in burn injury.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Design and synthesis of novel sEH inhibitors for the treatment of acute lung injury.European journal of medicinal chemistry · 2026Article
- Oxidized metabolites of linoleic acid as biomarkers of pancreatic beta-cell function in the first-onset type 2 diabetic patients with obesity.Journal of endocrinological investigation · 2026Article
- Soluble Epoxide Hydrolase Inhibitors Improve Cornea Alkali Wound Healing.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Soluble epoxide hydrolase in the liver orchestrates abdominal aortic aneurysm formation in mice.Communications biology · 2026Article
- Metabolic alteration in oxylipins and endocannabinoids point to an important role for soluble epoxide hydrolase and inflammation in Alzheimer's disease-finding from Alzheimer's Disease Neuroimaging Initiative.Alzheimer's research & therapy · 2026Article
- Molecular mechanisms and clinical significance of the glioma metabolic-immune axis: a comprehensive review.Frontiers in immunology · 2026Review
- Integrated serum metabolomics reveals severity-associated exploratory metabolic signatures in burn patients.Frontiers in physiology · 2026Article
- Genetically Predicted 12,13-DiHOME Mediates the Association between TNF-Related Apoptosis-Inducing Ligand and Immune Thrombocytopenia.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Disturbance of Oxylipin Metabolism Mediated by Autophagy of Mesenteric Adipocytes Orchestrates Gut Inflammation in Crohn's Disease.Cellular and molecular gastroenterology and hepatology · 2026Article
- Cytokine and Oxylipin Production in Resting and LPS-Stimulated Monocytes From Americans of African Ancestry Are Influenced by ALOX5 Promoter Tandem Repeat Polymorphisms.Mediators of inflammation · 2026Article
- Article
- Development of a Liquid Chromatography-Tandem Mass Spectrometry Method for Oxylipin Analysis and Its Application to Children's Plasma.Diagnostics (Basel, Switzerland) · 2025Article
- Sphingolipid metabolism-related genes for the diagnosis of metabolic syndrome by integrated bioinformatics analysis and Mendelian randomization identification.Diabetology & metabolic syndrome · 2025Article
- The Octadecanoids: Synthesis and Bioactivity of 18-Carbon Oxygenated Fatty Acids in Mammals, Bacteria, and Fungi.Chemical reviews · 2025Review
- Dynamics of oxylipin biosynthesis in systemic inflammation: insights from a large animal model of endotoxemia.Frontiers in immunology · 2025Article
- Inhibition of soluble epoxide hydrolase in endotoxin induced pig lung injury.Frontiers in pharmacology · 2025Article
- The platelet and plasma proteome and targeted lipidome in postpartum dairy cows with elevated systemic inflammation.Scientific reports · 2024Article
- Oxylipins Derived from PUFAs in Cardiometabolic Diseases: Mechanism of Actions and Possible Nutritional Interactions.Nutrients · 2024Review
- A regulatory loop involving the cytochrome P450-soluble epoxide hydrolase axis and TGF-β signaling.iScience · 2024Article
- Effects of sEH inhibition on the eicosanoid and cytokine storms in SARS-CoV-2-infected mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Fatty acid composition in the Western diet has shifted from saturated to polyunsaturated fatty acids (PUFAs), and specifically to linoleic acid (LA, 18:2), which has gradually increased in the diet over the past 50 y to become the most abundant dietary fatty acid in human adipose tissue. PUFA-derived oxylipins regulate a variety of biological functions. The cytochrome P450 (CYP450)–formed epoxy fatty acid metabolites of LA (EpOMEs) are hydrolyzed by the soluble epoxide hydrolase enzyme (sEH) to dihydroxyoctadecenoic acids (DiHOMEs). DiHOMEs are considered cardioprotective at low concentrations but at higher levels have been implicated as vascular permeability and cytotoxic agents and are associated with acute respiratory distress syndrome in severe COVID-19 patients. High EpOME levels have also correlated with sepsis-related fatalities; however, those studies failed to monitor DiHOME levels. Considering the overlap of burn pathophysiology with these pathologies, the role of DiHOMEs in the immune response to burn injury was investigated. 12,13-DiHOME was found to facilitate the maturation and activation of stimulated neutrophils, while impeding monocyte and macrophage functionality and cytokine generation. In addition, DiHOME serum concentrations were significantly elevated in burn-injured mice and these increases were ablated by administration of 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a sEH inhibitor. TPPU also reduced necrosis of innate and adaptive immune cells in burned mice, in a dose-dependent manner. The findings suggest DiHOMEs are a key driver of immune cell dysfunction in severe burn injury through hyperinflammatory neutrophilic and impaired monocytic actions, and inhibition of sEH might be a promising therapeutic strategy to mitigate deleterious outcomes in burn patients.
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