ArticlePloS one2016
Myeloid Cell Prostaglandin E2 Receptor EP4 Modulates Cytokine Production but Not Atherogenesis in a Mouse Model of Type 1 Diabetes.
Article in PloS one, 2016. 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, 22 citations in OpenAlex.
- The update of prostaglandin E2 receptor subtype 4 (EP4) in inflammatory diseases.Genes & diseases · 2026Review
- Article
- Dynamic changes in macrophage populations and resulting alterations in Prostaglandin ECell communication and signaling : CCS · 2025Article
- Investigating the role of the mPGES-PGE₂-EP4 pathway inFrontiers in veterinary science · 2025Article
- Disruption of the PGEbioRxiv : the preprint server for biology · 2024Article
- Prostanoids in Cardiac and Vascular Remodeling.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- The Evolving Role of Dendritic Cells in Atherosclerosis.International journal of molecular sciences · 2024Review
- Role of EP4 factor in paediatric type 1 diabetes mellitus: a comprehensive review focusing on the honeymoon period.Pediatric endocrinology, diabetes, and metabolism · 2024Review
- Harnessing prostaglandin ETrends in immunology · 2023Review
- Crystalline silica-induced proinflammatory eicosanoid storm in novel alveolar macrophage model quelled by docosahexaenoic acid supplementation.Frontiers in immunology · 2023Article
- The Remnant Lipoprotein Hypothesis of Diabetes-Associated Cardiovascular Disease.Arteriosclerosis, thrombosis, and vascular biology · 2022Review
- Review
- Enhanced Palmitate-Induced Interleukin-8 Formation in Human Macrophages by Insulin or Prostaglandin EBiomedicines · 2021Article
- Wnt signaling enhances macrophage responses to IL-4 and promotes resolution of atherosclerosis.eLife · 2021Article
- Platelet-conditioned media induces an anti-inflammatory macrophage phenotype through EP4.Journal of thrombosis and haemostasis : JTH · 2021Article
- International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin EPharmacological reviews · 2020Article
- Myocardial Infarction Does Not Accelerate Atherosclerosis in a Mouse Model of Type 1 Diabetes.Diabetes · 2020Article
- Eicosanoids: Atherosclerosis and cardiometabolic health.Journal of clinical & translational endocrinology · 2020Review
- Monocytes and Macrophages as Protagonists in Vascular Complications of Diabetes.Frontiers in cardiovascular medicine · 2020Review
- Restoration of the type I IFN-IL-1 balance through targeted blockade of PTGER4 inhibits autoimmunity in NOD mice.JCI insight · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Type 1 diabetes mellitus (T1DM) is associated with cardiovascular complications induced by atherosclerosis. Prostaglandin E2 (PGE2) is often raised in states of inflammation, including diabetes, and regulates inflammatory processes. In myeloid cells, a key cell type in atherosclerosis, PGE2 acts predominately through its Prostaglandin E Receptor 4 (EP4; Ptger4) to modulate inflammation. The effect of PGE2-mediated EP4 signaling specifically in myeloid cells on atherosclerosis in the presence and absence of diabetes is unknown. Because diabetes promotes atherosclerosis through increased arterial myeloid cell accumulation, we generated a myeloid cell-targeted EP4-deficient mouse model (EP4M-/-) of T1DM-accelerated atherogenesis to investigate the relationship between myeloid cell EP4, inflammatory phenotypes of myeloid cells, and atherogenesis. Diabetic mice exhibited elevated plasma PGE metabolite levels and elevated Ptger4 mRNA in macrophages, as compared with non-diabetic littermates. PGE2 increased Il6, Il1b, Il23 and Ccr7 mRNA while reducing Tnfa mRNA through EP4 in isolated myeloid cells. Consistently, the stimulatory effect of diabetes on peritoneal macrophage Il6 was mediated by PGE2-EP4, while PGE2-EP4 suppressed the effect of diabetes on Tnfa in these cells. In addition, diabetes exerted effects independent of myeloid cell EP4, including a reduction in macrophage Ccr7 levels and increased early atherogenesis characterized by relative lesional macrophage accumulation. These studies suggest that this mouse model of T1DM is associated with increased myeloid cell PGE2-EP4 signaling, which is required for the stimulatory effect of diabetes on IL-6, markedly blunts the effect of diabetes on TNF-α and does not modulate diabetes-accelerated atherogenesis.
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