ArticleScientific reports2020
Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes/macrophages induced by TNF-α.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 60 citations in OpenAlex.
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- Sphingolipid Metabolism Links Morphological Signatures to Immunomodulatory Potency in Human Mesenchymal Stromal Cells.Cellular and molecular bioengineering · 2026Article
- The immunogenetic basis of ovarian apoptosis: from TNF-α polymorphisms and signaling pathways to glucocorticoid-mediated rescue.Journal of ovarian research · 2026Review
- Neutral sphingomyelinases restrict natural killer cells activity against lung cancer.Cancer immunology, immunotherapy : CII · 2026Article
- Macrophage Plg-RJournal of thrombosis and haemostasis : JTH · 2026Article
- Ceramides may Play a Central Role in the Pathogenesis of Alzheimer's Disease: a Review of Evidence and Horizons for Discovery.Molecular neurobiology · 2025Review
- Ceramides in non-communicable diseases: pathways, nutritional modulation, and therapeutic opportunities.Journal of physiology and biochemistry · 2025Review
- Glucocorticoids regulate small extracellular vesicle (sEV) release via activation of nSMase2.bioRxiv : the preprint server for biology · 2025Article
- The Interplay Between Oxidative Stress and Lipid Composition in Obesity-Induced Inflammation: Antioxidants as Therapeutic Agents in Metabolic Diseases.International journal of molecular sciences · 2025Review
- The role of exosomal PD-L1 in NSCLC immunotherapy.Immunotherapy · 2025Review
- Protective Effects of COG133 on Carbon Tetrachloride-Induced Acute Liver Injury: Modulation of Inflammation, Apoptosis and Sphingolipid Metabolism.Journal of cellular and molecular medicine · 2025Article
- Extracellular vesicles in age-related diseases: disease pathogenesis, intervention, and biomarker.Stem cell research & therapy · 2025Review
- Alaska's Flora as a Treatment for Cancer.International journal of biopharmaceutical sciences · 2024Article
- Omega-3 supplementation attenuates doxorubicin-induced cardiotoxicity but is not related to the ceramide pathway.Food science & nutrition · 2024Article
- The multiple roles of chronic stress and glucocorticoids in Alzheimer's disease pathogenesis.Trends in neurosciences · 2024Review
- Plasma ceramides as biomarkers for microvascular disease and clinical outcomes in diabetes and myocardial infarction.Clinical diabetes and endocrinology · 2024Article
- ATF4 Contributes to Abdominal Aortic Aneurysm Formation via Modulating M1 Macrophage Polarization and Inflammation.Aging and disease · 2024Article
- Multi-Omics Reveals Disrupted Immunometabolic Homeostasis and Oxidative Stress in Adipose Tissue of Dairy Cows with Subclinical Ketosis: A Sphingolipid-Centric Perspective.Antioxidants (Basel, Switzerland) · 2024Article
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Obesity is associated with elevated levels of TNF-α and proinflammatory CD11c monocytes/macrophages. TNF-α mediated dysregulation in the plasticity of monocytes/macrophages is concomitant with pathogenesis of several inflammatory diseases, including metabolic syndrome, but the underlying mechanisms are incompletely understood. Since neutral sphingomyelinase-2 (nSMase2: SMPD3) is a key enzyme for ceramide production involved in inflammation, we investigated whether nSMase2 contributed to the inflammatory changes in the monocytes/macrophages induced by TNF-α. In this study, we demonstrate that the disruption of nSMase activity in monocytes/macrophages either by chemical inhibitor GW4869 or small interfering RNA (siRNA) against SMPD3 results in defects in the TNF-α mediated expression of CD11c. Furthermore, blockage of nSMase in monocytes/macrophages inhibited the secretion of inflammatory mediators IL-1β and MCP-1. In contrast, inhibition of acid SMase (aSMase) activity did not attenuate CD11c expression or secretion of IL-1β and MCP-1. TNF-α-induced phosphorylation of JNK, p38 and NF-κB was also attenuated by the inhibition of nSMase2. Moreover, NF-kB/AP-1 activity was blocked by the inhibition of nSMase2. SMPD3 was elevated in PBMCs from obese individuals and positively corelated with TNF-α gene expression. These findings indicate that nSMase2 acts, at least in part, as a master switch in the TNF-α mediated inflammatory responses in monocytes/macrophages.
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Registered trials
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