ArticlePloS one2011
Endogenous epoxygenases are modulators of monocyte/macrophage activity.
Article in PloS one, 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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Who cites it
44 citing papers in PubMed, 82 citations in OpenAlex.
- Trial
- From Strain to Repair: A Targeted Review of Lipid Mediators Driving the Inflammatory Cascade Following Exercise.Sports medicine (Auckland, N.Z.) · 2026Review
- Review
- Intraperitoneally injected d11-11(12)-epoxyeicosatrienoic acid is rapidly incorporated and esterified within rat plasma and peripheral tissues but not the brain.Prostaglandins, leukotrienes, and essential fatty acids · 2024Article
- Eicosanoid-Regulated Myeloid ENaC and Isolevuglandin Formation in Human Salt-Sensitive Hypertension.Hypertension (Dallas, Tex. : 1979) · 2024Article
- The interplay of inflammation and placenta in maternal diabetes: insights into Hofbauer cell expression patterns.Frontiers in immunology · 2024Article
- The soluble epoxide hydrolase inhibitor TPPU improves comorbidity of chronic pain and depression via the AHR and TSPO signaling.Journal of translational medicine · 2023Article
- Anti-Inflammatory Role of TRPV4 in Human Macrophages.ImmunoHorizons · 2023Article
- The anti-inflammatory role of placental Hofbauer cells is altered in patients with chorioamnionitis: Are CYP2C8 and soluble epoxide hydrolase involved in immunomodulation?Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2022Article
- Orally active epoxyeicosatrienoic acid analogs in hypertension and renal injury.Advances in pharmacology (San Diego, Calif.) · 2022Article
- sEH promotes macrophage phagocytosis and lung clearance of Streptococcus pneumoniae.The Journal of clinical investigation · 2021Article
- Cross-Sectional Estimation of Endogenous Biomarker Associations with Prenatal Phenols, Phthalates, Metals, and Polycyclic Aromatic Hydrocarbons in Single-Pollutant and Mixtures Analysis Approaches.Environmental health perspectives · 2021Article
- Targeting arachidonic acid-related metabolites in COVID-19 patients: potential use of drug-loaded nanoparticles.Emergent materials · 2021Review
- The Role of Epoxyeicosatrienoic Acids in Cardiac Remodeling.Frontiers in physiology · 2021Review
- Lipid Profile of Activated Macrophages and Contribution of Group V Phospholipase ABiomolecules · 2020Article
- An epoxide hydrolase inhibitor reduces neuroinflammation in a mouse model of Alzheimer's disease.Science translational medicine · 2020Article
- Exploring the molecular approach of COX and LOX in Alzheimer's and Parkinson's disorder.Molecular biology reports · 2020Review
- Peripheral soluble epoxide hydrolase inhibition reduces hypernociception and inflammation in albumin-induced arthritis in temporomandibular joint of rats.International immunopharmacology · 2020Article
- sEH Inhibitor Tppu Ameliorates Cecal Ligation and Puncture-Induced Sepsis by Regulating Macrophage Functions.Shock (Augusta, Ga.) · 2020Article
- Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundArachidonic acid is metabolized through three major metabolic pathways, the cyclooxygenase, lipoxygenase and CYP450 enzyme systems. Unlike cyclooxygenase and lipoxygenases, the role of CYP450 epoxygenases in monocyte/macrophage-mediated responses is not known. METHODOLOGY/PRINCIPAL
findingsWhen transfected in vitro, CYP2J2 is an efficient activator of anti-inflammatory pathways through the nuclear receptor peroxisome proliferator-activated receptor (PPAR) α. Human monocytes and macrophages contain PPARα and here we show they express the epoxygenases CYP2J2 and CYP2C8. Inhibition of constitutive monocyte epoxygenases using the epoxygenase inhibitor SKF525A induces cyclooxygenase (COX)-2 expression and activity, and the release of TNFα, and can be reversed by either add back of the endogenous epoxygenase products and PPARα ligand 11,12- epoxyeicosatrienoic acid (EET) or the addition of the selective synthetic PPARα ligand GW7647. In alternatively activated (IL-4-treated) monocytes, in contrast to classically activated cells, epoxygenase inhibition decreased TNFα release. Epoxygenases can be pro-inflammatory via superoxide anion production. The suppression of TNFα by SKF525A in the presence of IL-4 was associated with a reduction in superoxide anion generation and reproduced by the superoxide dismutase MnCl(2). Similar to these acute activation studies, in monocyte derived macrophages, epoxygenase inhibition elevates M1 macrophage TNFα mRNA and further decreases M2 macrophage TNFα. CONCLUSIONS/SIGNIFICANCE: In conclusion, epoxygenase activity represents an important endogenous pathway which limits monocyte activation. Moreover endogenous epoxygenases are immuno-modulators regulating monocyte/macrophage activation depending on the underlying activation state.
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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.