ArticleShock (Augusta, Ga.)2020
sEH Inhibitor Tppu Ameliorates Cecal Ligation and Puncture-Induced Sepsis by Regulating Macrophage Functions.
Article in Shock (Augusta, Ga.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Inhibitors of soluble epoxide hydrolase on acute lung injury: a meta-analysis of preclinical studies.Inflammopharmacology · 2022Pooled it
- Immune Regulatory and Underlying Mechanisms of Polysaccharides fromMolecules (Basel, Switzerland) · 2026Article
- Cytochrome P450-derived Epoxyeicosatrienoic Acid, the Regulation of Cardiovascular-related Diseases, and the Implication for Pulmonary Hypertension.Cardiovascular drugs and therapy · 2025Review
- Article
- Comprehensive single-cell analysis deciphered the immunoregulatory mechanism of TPPU in alleviating sepsis-related acute liver injury.Journal of advanced research · 2025Article
- Enhancing cancer immunotherapy via inhibition of soluble epoxide hydrolase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Unveiling the immunomodulator role of plasma oxidized lipids in SA-AKI progression: a CRRT perspective.Frontiers in physiology · 2024Article
- Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis.Clinical immunology (Orlando, Fla.) · 2023Article
- Genetic deletion or pharmacological inhibition of soluble epoxide hydrolase attenuated particulate matter 2.5 exposure mediated lung injury.Journal of hazardous materials · 2023Article
- Aflatoxin BEcotoxicology and environmental safety · 2023Article
- Lipidome modulation by dietary omega-3 polyunsaturated fatty acid supplementation or selective soluble epoxide hydrolase inhibition suppresses rough LPS-accelerated glomerulonephritis in lupus-prone mice.Frontiers in immunology · 2023Article
- CYP450 Epoxygenase Metabolites, Epoxyeicosatrienoic Acids, as Novel Anti-Inflammatory Mediators.Molecules (Basel, Switzerland) · 2022Review
- A Novel Role for Cytochrome P450 Epoxygenase Metabolites in Septic Shock.Critical care explorations · 2022Article
- Inhibition of Soluble Epoxide Hydrolase Attenuates Bosutinib-Induced Blood Pressure Elevation.Hypertension (Dallas, Tex. : 1979) · 2021Article
- Epoxyeicosatrienoic Acids and Fibrosis: Recent Insights for the Novel Therapeutic Strategies.International journal of molecular sciences · 2021Review
- TPPU treatment of burned mice dampens inflammation and generation of bioactive DHET which impairs neutrophil function.Scientific reports · 2021Article
- Pharmacological inhibition of soluble epoxide hydrolase attenuates chronic experimental autoimmune encephalomyelitis by modulating inflammatory and anti-inflammatory pathways in an inflammasome-dependent and -independent manner.Inflammopharmacology · 2020Article
- Soluble epoxide hydrolase inhibitor, TPPU, increases regulatory T cells pathway in an arthritis model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Soluble Epoxide Hydrolase Inhibition in Liver Diseases: A Review of Current Research and Knowledge Gaps.Biology · 2020Review
- Prolonged Soluble Epoxide Hydrolase Reactivity in Brain Endothelial Cells Is Associated with Long Cognitive Deficits in Sepsis.Molecular neurobiology · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSepsis is a life-threatening organ dysfunction initiated by a dysregulated response to infection, with imbalanced inflammation and immune homeostasis. Macrophages play a pivotal role in sepsis. N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl)-urea (TPPU) is an inhibitor of soluble epoxide hydrolase (sEH), which can rapidly hydrolyze epoxyeicosatrienoic acids (EETs) to the bio-inactive dihydroxyeicosatrienoic acids. TPPU was linked with the regulation of macrophages and inflammation. Here, we hypothesized that sEH inhibitor TPPU ameliorates cecal ligation and puncture (CLP)-induced sepsis by regulating macrophage functions.
methodsA polymicrobial sepsis model induced by CLP was used in our study. C57BL/6 mice were divided into four groups: sham+ phosphate buffer saline (PBS), sham+TPPU, CLP+PBS, CLP+TPPU. Mice were observed 48 h after surgery to assess the survival rate. For other histological examinations, mice were sacrificed 6 h after surgery. Macrophage cell line RAW264.7 was used for in vitro studies.
resultsTPPU treatment, accompanied with increased EETs levels, markedly improved the survival of septic mice induced by CLP surgery, which was associated with alleviated organ damage and dysfunction triggered by systemic inflammatory response. Moreover, TPPU treatment significantly inhibited systemic inflammatory response via EETs-induced inactivation of mitogen-activated protein kinase signaling due to enhanced macrophage phagocytic ability and subsequently reduced bacterial proliferation and dissemination, and decreased inflammatory factors release.
conclusionsEH inhibitor TPPU ameliorates cecal ligation and puncture-induced sepsis by regulating macrophage functions, including improved phagocytosis and reduced inflammatory response. Our data indicate that sEH inhibition has potential therapeutic effects on polymicrobial-induced sepsis.
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