ArticleThe Journal of allergy and clinical immunology2016
Leukotriene D4 and prostaglandin E2 signals synergize and potentiate vascular inflammation in a mast cell-dependent manner through cysteinyl leukotriene receptor 1 and E-prostanoid receptor 3.
Article in The Journal of allergy and clinical immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 72 citations in OpenAlex.
- DPEP2 suppresses hyperinflammation via metabolic reprogramming of macrophages in sepsis.Nature communications · 2026Article
- Leukotrienes: Bridging the Inflammatory Gap in Asthma and Inflammatory Bowel Diseases (IBD).Comprehensive Physiology · 2025Review
- The anti-inflammatory drug Montelukast ameliorates cognitive deficits by rescuing the inflammatory levels in young AD animal models.Scientific reports · 2025Article
- Determination of nine prostaglandins in the arachidonic acid metabolic pathway with UHPLC-QQQ-MS/MS and application toFrontiers in pharmacology · 2025Article
- Biocomputational screening of natural compounds targeting 15-hydroxyprostaglandin dehydrogenase to improve skeletal muscle during aging.Molecular diversity · 2024Article
- Prostaglandin and prostaglandin receptors: present and future promising therapeutic targets for pulmonary arterial hypertension.Respiratory research · 2023Review
- Epigenetic histone modification by butyrate downregulates KIT and attenuates mast cell function.Journal of cellular and molecular medicine · 2023Article
- Superior protective effects of PGE2 priming mesenchymal stem cells against LPS-induced acute lung injury (ALI) through macrophage immunomodulation.Stem cell research & therapy · 2023Article
- St13 protects against disordered acinar cell arachidonic acid pathway in chronic pancreatitis.Journal of translational medicine · 2022Article
- The role of human mast cells in allergy and asthma.Bioengineered · 2022Review
- Identification of Transcriptomic Differences between Lower Extremities Arterial Disease, Abdominal Aortic Aneurysm and Chronic Venous Disease in Peripheral Blood Mononuclear Cells Specimens.International journal of molecular sciences · 2021Article
- Role of prostaglandin E2 in tissue repair and regeneration.Theranostics · 2021Review
- Leukotriene DFrontiers in physiology · 2021Article
- Review
- Untargeted lipidomics reveals progression of early Alzheimer's disease in APP/PS1 transgenic mice.Scientific reports · 2020Article
- A molecular map of murine lymph node blood vascular endothelium at single cell resolution.Nature communications · 2020Article
- Montelukast Prevents Mice Against Acetaminophen-Induced Liver Injury.Frontiers in pharmacology · 2019Article
- Prostaglandins in asthma and allergic diseases.Pharmacology & therapeutics · 2019Review
- Raf kinase inhibitor protein negatively regulates FcεRI-mediated mast cell activation and allergic response.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Role of oxidized lipids in pulmonary arterial hypertension.Pulmonary circulation · 2016Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAlthough arachidonic acid metabolites, cysteinyl leukotrienes (cys-LTs; leukotriene [LT] C4, LTD4, and LTE4), and prostaglandin (PG) E2 are generated at the site of inflammation, it is not known whether crosstalk exists between these 2 classes of inflammatory mediators.
objectiveWe sought to determine the role of LTD4-PGE2 crosstalk in inducing vascular inflammation in vivo, identify effector cells, and ascertain specific receptors and pathways involved in vitro.
methodsVascular (ear) inflammation was assessed by injecting agonists into mouse ears, followed by measuring ear thickness and histology, calcium influx with Fura-2, phosphorylation and expression of signaling molecules by means of immunoblotting, PGD2 and macrophage inflammatory protein 1β generation by using ELISA, and expression of transcripts by using RT-PCR. Candidate receptors and signaling molecules were identified by using antagonists and inhibitors and confirmed by using small interfering RNA.
resultsLTD4 plus PGE2 potentiated vascular permeability and edema, gearing the system toward proinflammation in wild-type mice but not in Kit(W-sh) mice. Furthermore, LTD4 plus PGE2, through cysteinyl leukotriene receptor 1 (CysLT1R) and E-prostanoid receptor (EP) 3, enhanced extracellular signal-regulated kinase (Erk) and c-fos phosphorylation, inflammatory gene expression, macrophage inflammatory protein 1β secretion, COX-2 upregulation, and PGD2 generation in mast cells. Additionally, we uncovered that this synergism is mediated through Gi, protein kinase G, and Erk signaling. LTD4 plus PGE2-potentiated effects are partially sensitive to CysLT1R or EP3 antagonists but completely abolished by simultaneous treatment both in vitro and in vivo.
conclusionsOur results unravel a unique LTD4-PGE2 interaction affecting mast cells through CysLT1R and EP3 involving Gi, protein kinase G, and Erk and contributing to vascular inflammation in vivo. Furthermore, current results also suggest an advantage of targeting both CysLT1R and EP3 in attenuating inflammation.
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