ArticleProceedings of the National Academy of Sciences of the United States of America2014
Phospholipase A2 regulates eicosanoid class switching during inflammasome activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 3 of them syntheses that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
100 citing papers in PubMed, 3 syntheses or guidelines pooled it, 140 citations in OpenAlex.
- Targeting Mammalian 5-Lipoxygenase by Dietary Phenolics as an Anti-Inflammatory Mechanism: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Evaluation of the arachidonic acid pathway in bipolar disorder: a systematic review.Molecular biology reports · 2020Pooled it
- Regulation of Intestinal Inflammation by Dietary Fats.Frontiers in immunology · 2020Pooled it
- Cutting Edge: Severe SARS-CoV-2 Infection in Humans Is Defined by a Shift in the Serum Lipidome, Resulting in Dysregulation of Eicosanoid Immune Mediators.Journal of immunology (Baltimore, Md. : 1950) · 2021Trial
- Phospholipases: Where Do We Stand?Methods in molecular biology (Clifton, N.J.) · 2027Review
- The Phospholipase AJournal of lipid and atherosclerosis · 2026Review
- Microglial 5-LOX-activating protein antagonism alleviates leukotriene-driven neuroinflammation.Acta neuropathologica · 2026Article
- Sepsis-associated acute lung injury: do inflammatory lipid mediators flood the lungs by activating pulmonary TRP channels?Intensive care medicine experimental · 2026Review
- Precisely designed keystone metabolites boost shrimp disease resistance by recruiting symbionts via the lipoxin A4-AP-1 pathway.Microbiome · 2026Article
- Loss of calcium-dependent phospholipase A2 contributes to multi-omic changes in mouse denervated skeletal muscle.Physiological reports · 2026Article
- Buckwheat Flavonoids Modulate Inflammation in RAW 264.7 Macrophages at Physiologically Relevant Concentrations via the LPS/COX-2 Pathway.Journal of agricultural and food chemistry · 2026Article
- Elucidation of a potent pro-resolving mediator of inflammation resolution via human neutrophil-vascular endothelial cell interactions.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Lipid remodeling and circulating semaphorin 3A in diminished ovarian reserve.Scientific reports · 2026Article
- MSC administration resolves experimental acute gout increasing specialized pro-resolving mediators synthesis through a super-induction of prostaglandin EStem cell research & therapy · 2025Article
- Nouveau benzo-mimetics of 17R-Resolvin D2 are potent resolution agonists for inflammation.iScience · 2025Article
- COVID-19 is Associated with a Lipid Storm that Worsens in Cases of Severe Pneumonia.Microorganisms · 2025Article
- LPCAT3-dependent remodeling of the phospholipids and lipid rafts is essential for vascular proinflammatory signaling and the development of atherosclerosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Chilling injury mechanism in the immature oocytes of zebrafish (Danio rerio).The Journal of reproduction and development · 2025Article
- The mechanism of heat stress-induced injury in the immature oocytes of zebrafish (Danio rerio).The Journal of reproduction and development · 2025Article
- Neutrophils secrete exosome-associated DNA to resolve sterile acute inflammation.Nature cell biology · 2025Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Initiation and resolution of inflammation are considered to be tightly connected processes. Lipoxins (LX) are proresolution lipid mediators that inhibit phlogistic neutrophil recruitment and promote wound-healing macrophage recruitment in humans via potent and specific signaling through the LXA4 receptor (ALX). One model of lipoxin biosynthesis involves sequential metabolism of arachidonic acid by two cell types expressing a combined transcellular metabolon. It is currently unclear how lipoxins are efficiently formed from precursors or if they are directly generated after receptor-mediated inflammatory commitment. Here, we provide evidence for a pathway by which lipoxins are generated in macrophages as a consequence of sequential activation of toll-like receptor 4 (TLR4), a receptor for endotoxin, and P2X7, a purinergic receptor for extracellular ATP. Initial activation of TLR4 results in accumulation of the cyclooxygenase-2-derived lipoxin precursor 15-hydroxyeicosatetraenoic acid (15-HETE) in esterified form within membrane phospholipids, which can be enhanced by aspirin (ASA) treatment. Subsequent activation of P2X7 results in efficient hydrolysis of 15-HETE from membrane phospholipids by group IVA cytosolic phospholipase A2, and its conversion to bioactive lipoxins by 5-lipoxygenase. Our results demonstrate how a single immune cell can store a proresolving lipid precursor and then release it for bioactive maturation and secretion, conceptually similar to the production and inflammasome-dependent maturation of the proinflammatory IL-1 family cytokines. These findings provide evidence for receptor-specific and combinatorial control of pro- and anti-inflammatory eicosanoid biosynthesis, and potential avenues to modulate inflammatory indices without inhibiting downstream eicosanoid pathways.
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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.