ArticleProceedings of the National Academy of Sciences of the United States of America2023
Glucocorticoids regulate lipid mediator networks by reciprocal modulation of 15-lipoxygenase isoforms affecting inflammation resolution.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. 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, 28 citations in OpenAlex.
- Complementary Regulation of Inflammatory, Catabolic, and PPARγ Signaling by Dexamethasone and Decanoic Acid in Donor-Specific Human Chondrocyte Models.Biomedicines · 2026Article
- Tocotrienol metabolites redirect lipid mediator production in innate immune cells towards inflammation resolution.Acta pharmaceutica Sinica. B · 2026Article
- Social isolation of aged mice drives dramatic release of inflammatory lipoxygenase-derived oxylipins.npj aging · 2026Article
- Chromatin dynamics identifies 78 genes at loci associated with elevated intraocular pressure and primary open-angle glaucoma.bioRxiv : the preprint server for biology · 2026Article
- Timing of Glucocorticoid Treatment Dictates Glucocorticoid Receptor Actions Modulating the NLRP3-Inflammasome Activation in Macrophages.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Chronic enteritis triggered by diet westernization is driven by epithelial ATG16L1-mediated autophagy.Autophagy · 2026Article
- Monitoring early micro-oxidation under refrigeration: iron and oxidative markers predict quality loss in grass carp.Current research in food science · 2026Article
- MSC administration resolves experimental acute gout increasing specialized pro-resolving mediators synthesis through a super-induction of prostaglandin EStem cell research & therapy · 2025Article
- Up-regulation of Ifi27l2a expression in bone marrow monocytes contributes to glucocorticoid-induced bone loss.Communications biology · 2025Article
- Alkylglycerol monooxygenase represses prostanoid biosynthesis in a sex-dependent manner.Cell & bioscience · 2025Article
- Endogenous glucocorticoids and human immunity: Time to revisit old dogmas.Seminars in immunology · 2025Review
- Development and validation of a prediction model for cholangitis after percutaneous transhepatic cholangioscopic lithotripsy.Clinical and experimental medicine · 2025Article
- Proresolving Lipid Mediators in the Respiratory System.Annual review of physiology · 2025Review
- Study on the therapeutic effect of Viola yedoensis and Leonurus japonicus on bovine endometritis.Journal of animal science · 2025Article
- Article
- Nomogram for Predicting Sepsis After Percutaneous Transhepatic Cholangioscopic Lithotripsy.Journal of inflammation research · 2025Article
- Multiparametric analysis in the peripheral blood of Giant Cell Arteritis and Polymyalgia Rheumatica patients at the early phases of steroid treatment reveals changes in cell subpopulations and lipid mediators: a preliminary study.Frontiers in immunology · 2025Article
- Ubiquitination regulation of mitochondrial homeostasis: a new sight for the treatment of gastrointestinal tumors.Frontiers in immunology · 2025Review
- Omega-3 and Sports: Focus on Inflammation.Life (Basel, Switzerland) · 2024Review
- Development and Validation of Methodologies for the Identification of Specialized Pro-Resolving Lipid Mediators and Classic Eicosanoids in Biological Matrices.Journal of the American Society for Mass Spectrometry · 2024Article
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Glucocorticoids (GC) are potent anti-inflammatory agents, broadly used to treat acute and chronic inflammatory diseases, e.g., critically ill COVID-19 patients or patients with chronic inflammatory bowel diseases. GC not only limit inflammation but also promote its resolution although the underlying mechanisms are obscure. Here, we reveal reciprocal regulation of 15-lipoxygenase (LOX) isoform expression in human monocyte/macrophage lineages by GC with respective consequences for the biosynthesis of specialized proresolving mediators (SPM) and their 15-LOX-derived monohydroxylated precursors (mono-15-OH). Dexamethasone robustly up-regulated pre-mRNA, mRNA, and protein levels of ALOX15B/15-LOX-2 in blood monocyte-derived macrophage (MDM) phenotypes, causing elevated SPM and mono-15-OH production in inflammatory cell types. In sharp contrast, dexamethasone blocked ALOX15/15-LOX-1 expression and impaired SPM formation in proresolving M2-MDM. These dexamethasone actions were mimicked by prednisolone and hydrocortisone but not by progesterone, and they were counteracted by the GC receptor (GR) antagonist RU486. Chromatin immunoprecipitation (ChIP) assays revealed robust GR recruitment to a putative enhancer region within intron 3 of the ALOX15B gene but not to the transcription start site. Knockdown of 15-LOX-2 in M1-MDM abolished GC-induced SPM formation and mono-15-OH production. Finally, ALOX15B/15-LOX-2 upregulation was evident in human monocytes from patients with GC-treated COVID-19 or patients with IBD. Our findings may explain the proresolving GC actions and offer opportunities for optimizing GC pharmacotherapy and proresolving mediator production.
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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.