ArticlePloS one2018
Comparison of eight 15-lipoxygenase (LO) inhibitors on the biosynthesis of 15-LO metabolites by human neutrophils and eosinophils.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
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- Oxylipins in Atherosclerosis: Their Role in Inflammation, Diagnosis, and Therapeutic Perspectives.International journal of molecular sciences · 2025Review
- Species-specific optimization of oxylipin ionization in LC-MS: a design of experiments approach to improve sensitivity.Analytical and bioanalytical chemistry · 2025Article
- Unique effect of aspirin on local 15-oxo-eicosatetraenoic acid synthesis in asthma patients with aspirin hypersensitivity.Clinical and translational allergy · 2024Article
- Pharmacological evidence that the inhibitory effects of prostaglandin E2 are mediated by the EP2 and EP4 receptors in human neutrophils.Journal of leukocyte biology · 2024Article
- Synthesis of new multitarget-directed ligands containing thienopyrimidine nucleus for inhibition of 15-lipoxygenase, cyclooxygenases, and pro-inflammatory cytokines.European journal of medicinal chemistry · 2023Article
- Article
- Formation, Signaling and Occurrence of Specialized Pro-Resolving Lipid Mediators-What is the Evidence so far?Frontiers in pharmacology · 2022Review
- Identification of a Bromodomain-like Region in 15-Lipoxygenase-1 Explains Its Nuclear Localization.Angewandte Chemie (International ed. in English) · 2021Article
- Article
- Modulation of the Primary Astrocyte-Enriched Cultures' Oxylipin Profiles Reduces Neurotoxicity.Metabolites · 2021Article
- Deletion of Alox15 improves kidney dysfunction and inhibits fibrosis by increased PGDClinical and experimental nephrology · 2021Article
- Inflammatory heterogeneity in aspirin-exacerbated respiratory disease.The Journal of allergy and clinical immunology · 2021Article
- Progress in Understanding Ferroptosis and Its Targeting for Therapeutic Benefits in Traumatic Brain and Spinal Cord Injuries.Frontiers in cell and developmental biology · 2021Review
- Enhanced 15-Lipoxygenase 1 Production is Related to Periostin Expression and Eosinophil Recruitment in Eosinophilic Chronic Rhinosinusitis.Biomolecules · 2020Article
- Influence of Lipoxygenase Inhibition on Glioblastoma Cell Biology.International journal of molecular sciences · 2020Article
- A looming role of mitochondrial calcium in dictating the lung epithelial integrity and pathophysiology of lung diseases.Mitochondrion · 2020Review
- Non-targeted and targeted analysis of oxylipins in combination with charge-switch derivatization by ion mobility high-resolution mass spectrometry.Analytical and bioanalytical chemistry · 2020Article
- 15-Lipoxygenase-1 biosynthesis of 7S,14S-diHDHA implicates 15-lipoxygenase-2 in biosynthesis of resolvin D5.Journal of lipid research · 2020Article
- Targeting biosynthetic networks of the proinflammatory and proresolving lipid metabolome.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
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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
Neutrophils and eosinophils are important sources of bioactive lipids from the 5- and the 15-lipoxygenase (LO) pathways. Herein, we compared the effectiveness of humans eosinophils and eosinophil-depleted neutrophils to synthesize 15-LO metabolites using a cocktail of different 15-LO substrates as well as their sensitivities to eight documented 15-lipoxygenase inhibitors. The treatment of neutrophils and eosinophils with linoleic acid, dihomo-γ-linolenic acid, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid and arachidonyl-ethanolamide, led to the synthesis of 13-HODE, 15-HETrE, 15-HETE, 15-HEPE, 14-HDHA/17-HDHA, and 15-hydroxy-AEA. Neutrophils and eosinophils also metabolized the endocannabinoid 2-arachidonoyl-glycerol into 15-HETE-glycerol, although this required 2-arachidonoyl-glycerol hydrolysis inhibition. Neutrophils and eosinophils differed in regard to dihomo-γ-linolenic acid and linoleic acid utilization with 15-HETrE/13-HODE ratios of 0.014 ± 0.0008 and 0.474 ± 0.114 for neutrophils and eosinophils respectively. 15-LO metabolite synthesis by neutrophils and eosinophils also differed in regard to their relative production of 17-HDHA and 14-HDHA.The synthesis of 15-LO metabolites by neutrophils was concentration-dependent and rapid, reaching a plateau after one minute. While investigating the biosynthetic routes involved, we found that eosinophil-depleted neutrophils express the 15-lipoxygenase-2 but not the 15-LO-1, in contrast to eosinophils which express the 15-LO-1 but not the 15-LO-2. Moreover, 15-LO metabolite synthesis by neutrophils was not inhibited by the 15-LO-1 inhibitors BLX769, BLX3887, and ML351. However, 15-LO product synthesis was partially inhibited by 100 μM NDGA. Altogether, our data indicate that the best 15-LO-1 inhibitors in eosinophils are BLX3887, BLX769, NDGA and ML351 and that the synthesis of 15-LO metabolites by neutrophils does not involve the 15-LO-1 nor the phosphorylation of 5-LO on Ser-663 but is rather the consequence of 15-LO-2 or another unidentified 15-LO.
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