ArticlePloS one2013
Deletion of 12/15-lipoxygenase alters macrophage and islet function in NOD-Alox15(null) mice, leading to protection against type 1 diabetes development.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
- A review on the relationship between Arachidonic acid 15-Lipoxygenase (ALOX15) and diabetes mellitus.PeerJ · 2023Review
- Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes.Cell reports · 2022Article
- Review
- Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLAMolecules (Basel, Switzerland) · 2021Article
- 12-Lipoxygenase governs the innate immune pathogenesis of islet inflammation and autoimmune diabetes.JCI insight · 2021Article
- Regulation of Tissue Inflammation by 12-Lipoxygenases.Biomolecules · 2021Review
- The Impact of the CaBiomolecules · 2021Review
- Article
- Unexpected Cardiomyopathy and Cardiac Dysfunction after Administration of Sulfadiazine-trimethoprim Medicated Diet to ICR mice (Comparative medicine · 2020Article
- Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications.Pharmacology & therapeutics · 2019Review
- Genetic deletion of 12/15 lipoxygenase promotes effective resolution of inflammation following myocardial infarction.Journal of molecular and cellular cardiology · 2018Article
- Article
- Molecular mechanisms of nonalcoholic fatty liver disease: Potential role for 12-lipoxygenase.Journal of diabetes and its complications · 2017Review
- 12-Lipoxygenase Inhibitor Improves Functions of Cytokine-Treated Human Islets and Type 2 Diabetic Islets.The Journal of clinical endocrinology and metabolism · 2017Article
- Myeloid 12/15-LOX regulates B cell numbers and innate immune antibody levelsWellcome open research · 2017Article
- The Four-Way Stop Sign: Viruses, 12-Lipoxygenase, Islets, and Natural Killer Cells in Type 1 Diabetes Progression.Frontiers in endocrinology · 2017Article
- Host Factors Alter Effects of Angiopoietin-Like Protein 8 on Glucose Homeostasis in Diabetic Mice.Journal of diabetes mellitus · 2016Article
- Polarization of Macrophages toward M2 Phenotype Is Favored by Reduction in iPLA2β (Group VIA Phospholipase A2).The Journal of biological chemistry · 2016Article
- Lipids and immunoinflammatory pathways of beta cell destruction.Diabetologia · 2016Review
- 15-Lipoxygenase-1 Is Involved in the Effects of Atorvastatin on Endothelial Dysfunction.Mediators of inflammation · 2016Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsType 1 diabetes (T1D) is characterized by autoimmune depletion of insulin-producing pancreatic beta cells. We showed previously that deletion of the 12/15-lipoxygenase enzyme (12/15-LO, Alox15 gene) in NOD mice leads to nearly 100 percent protection from T1D. In this study, we test the hypothesis that cytokines involved in the IL-12/12/15-LO axis affect both macrophage and islet function, which contributes to the development of T1D.
methods12/15-LO expression was clarified in immune cells by qRT-PCR, and timing of expression was tested in islets using qRT-PCR and Western blotting. Expression of key proinflammatory cytokines and pancreatic transcription factors was studied in NOD and NOD-Alox15(null) macrophages and islets using qRT-PCR. The two mouse strains were also assessed for the ability of splenocytes to transfer diabetes in an adoptive transfer model, and beta cell mass.
results12/15-LO is expressed in macrophages, but not B and T cells of NOD mice. In macrophages, 12/15-LO deletion leads to decreased proinflammatory cytokine mRNA and protein levels. Furthermore, splenocytes from NOD-Alox15(null) mice are unable to transfer diabetes in an adoptive transfer model. In islets, expression of 12/15-LO in NOD mice peaks at a crucial time during insulitis development. The absence of 12/15-LO results in maintenance of islet health with respect to measurements of islet-specific transcription factors, markers of islet health, proinflammatory cytokines, and beta cell mass.
conclusionsThese results suggest that 12/15-LO affects islet and macrophage function, causing inflammation, and leading to autoimmunity and reduced beta cell mass.
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