ArticleFrontiers in immunology2018
A Novel Function for 15-Lipoxygenases in Cholesterol Homeostasis and CCL17 Production in Human Macrophages.
Article in Frontiers in immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- An integrated multiomics-based risk model for predicting the prognosis and immune microenvironment status in patients with papillary thyroid carcinoma.Gland surgery · 2026Article
- The role of ALOX15 in inflammation-related diseases.Frontiers in immunology · 2026Review
- RNAi-based ALOX15B silencing augments keratinocyte inflammation in vitro via EGFR/STAT1/JAK1 signalling.Cell death & disease · 2025Article
- Progress in macrophage immune regulation of atherosclerosis.American journal of translational research · 2025Review
- Efficacy and pharmacodynamic effect of anti-CD73 and anti-PD-L1 monoclonal antibodies in combination with cytotoxic therapy: observations from mouse tumor models.Cancer biology & therapy · 2024Article
- Murine Alox8 versus the human ALOX15B ortholog: differences and similarities.Pflugers Archiv : European journal of physiology · 2024Review
- Structural and Functional Biology of Mammalian ALOX Isoforms with Particular Emphasis on Enzyme Dimerization and Their Allosteric Properties.International journal of molecular sciences · 2024Review
- Spatial transcriptomics reveals altered lipid metabolism and inflammation-related gene expression of sebaceous glands in psoriasis and atopic dermatitis.Frontiers in immunology · 2024Article
- Multiple Shades of Gray-Macrophages in Acute Allograft Rejection.International journal of molecular sciences · 2023Review
- Ferroptosis in heart failure.Journal of molecular and cellular cardiology · 2022Review
- Integrated Analysis of Gut Microbiome and Lipid Metabolism in Mice Infected with Carbapenem-ResistantMetabolites · 2022Article
- Review
- Arachidonate 15-lipoxygenase type B: Regulation, function, and its role in pathophysiology.Frontiers in pharmacology · 2022Review
- Arachidonic Acid 15-Lipoxygenase: Effects of Its Expression, Metabolites, and Genetic and Epigenetic Variations on Airway Inflammation.Allergy, asthma & immunology research · 2021Review
- Ferroptosis: the potential value target in atherosclerosis.Cell death & disease · 2021Review
- The role of ferroptosis in breast cancer patients: a comprehensive analysis.Cell death discovery · 2021Article
- Diverse Immunoregulatory Roles of Oxysterols-The Oxidized Cholesterol Metabolites.Metabolites · 2020Review
- 15-Lipoxygenase-1 biosynthesis of 7S,14S-diHDHA implicates 15-lipoxygenase-2 in biosynthesis of resolvin D5.Journal of lipid research · 2020Article
- The interaction between ferroptosis and lipid metabolism in cancer.Signal transduction and targeted therapy · 2020Review
- The Biosynthesis of Enzymatically Oxidized Lipids.Frontiers in endocrinology · 2020Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arachidonate 15-lipoxygenase (ALOX15) and arachidonate 15-lipoxygenase, type B (ALOX15B) catalyze the dioxygenation of polyunsaturated fatty acids and are upregulated in human alternatively activated macrophages (AAMs) induced by Th2 cytokine interleukin-4 (IL-4) and/or interleukin-13. Known primarily for roles in bioactive lipid mediator synthesis, 15-lipoxygenases (15-LOXs) have been implicated in various macrophage functions including efferocytosis and ferroptosis. Using a combination of inhibitors and siRNAs to suppress 15-LOX isoforms, we studied the role of 15-LOXs in cellular cholesterol homeostasis and immune function in naïve and AAMs. Silencing or inhibiting the 15-LOX isoforms impaired sterol regulatory element binding protein (SREBP)-2 signaling by inhibiting SREBP-2 processing into mature transcription factor and reduced SREBP-2 binding to sterol regulatory elements and subsequent target gene expression. Silencing ALOX15B reduced cellular cholesterol and the cholesterol intermediates desmosterol, lanosterol, 24,25-dihydrolanosterol, and lathosterol as well as oxysterols in IL-4-stimulated macrophages. In addition, attenuating both 15-LOX isoforms did not generally affect IL-4 gene expression but rather uniquely impacted IL-4-induced CCL17 production in an SREBP-2-dependent manner resulting in reduced T cell migration to macrophage conditioned media. In conclusion, we identified a novel role for ALOX15B, and to a lesser extent ALOX15, in cholesterol homeostasis and CCL17 production in human macrophages.
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