ArticleImmunology2007
Acid sphingomyelinase inhibition suppresses lipopolysaccharide-mediated release of inflammatory cytokines from macrophages and protects against disease pathology in dextran sulphate sodium-induced colitis in mice.
Article in Immunology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 107 citations in OpenAlex.
- CD39 and CD161 modulate Th17 responses in Crohn's disease.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Causal Effects of Oral Microbiome, Circulating Metabolites, and Inflammatory Proteins on Recurrent Aphthous Stomatitis: A Two-Sample Mendelian Randomization Study.Oral health & preventive dentistry · 2026Article
- Sphingolipid Metabolism in Obesity: Bidirectional Regulation and Comparative Perspectives on Plant Sphingolipids.Nutrients · 2026Review
- Gut Microbiome-Sphingolipid Metabolism-Brain Axis Interactions: Neuroprotective Effects of Amitriptyline as Functional Inhibitor of Acid Sphingomyelinase in a Mouse Model of Tauopathy.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Metabolic regulation of gut barrier integrity in IBD: protein, lipid, and carbohydrate pathways.Frontiers in nutrition · 2026Review
- Tetraspanin-enriched membrane domains regulate vascular leakage by altering membrane cholesterol accessibility to balance antagonistic GTPases.Nature cardiovascular research · 2025Article
- Marked mucosal lipid shifts in treatment refractory inflammatory bowel disease: a lipidomic study.BMC gastroenterology · 2025Article
- Tissue factor-dependent colitogenic CD4Nature communications · 2025Article
- The Multifaceted Impact of Bioactive Lipids on Gut Health and Disease.International journal of molecular sciences · 2024Review
- Podocyte-specific silencing of acid sphingomyelinase gene to abrogate hyperhomocysteinemia-induced NLRP3 inflammasome activation and glomerular inflammation.American journal of physiology. Renal physiology · 2024Article
- Article
- Therapeutic Potential for Sphingolipids in Inflammatory Bowel Disease and Colorectal Cancer.Cancers · 2024Review
- Nanoparticle-Based Drug Delivery Systems for Inflammatory Bowel Disease Treatment.Drug design, development and therapy · 2024Review
- Inhibition of acid sphingomyelinase reduces reactive astrocyte secretion of mitotoxic extracellular vesicles and improves Alzheimer's disease pathology in the 5xFAD mouse.Acta neuropathologica communications · 2023Article
- Diverse Roles of Ceramide in the Progression and Pathogenesis of Alzheimer's Disease.Biomedicines · 2022Review
- Ceramide signaling in the gut.Molecular and cellular endocrinology · 2022Review
- Utilizing Sphingomyelinase Sensitizing Liposomes in Imaging Intestinal Inflammation in Dextran Sulfate Sodium-Induced Murine Colitis.Biomedicines · 2022Article
- Acid Sphingomyelinase Deficiency: A Clinical and Immunological Perspective.International journal of molecular sciences · 2021Review
- Fat of the Gut: Epithelial Phospholipids in Inflammatory Bowel Diseases.International journal of molecular sciences · 2021Review
- Relationship between Circulating Lipids and Cytokines in Metastatic Castration-Resistant Prostate Cancer.Cancers · 2021Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipopolysaccharide (LPS) and inflammatory cytokines cause activation of sphingomyelinases (SMases) and subsequent hydrolysis of sphingomyelin (SM) to produce a lipid messenger ceramide. The design of SMase inhibitors may offer new therapies for the treatment of LPS- and cytokine-related inflammatory bowel disease. We synthesized a series of difluoromethylene analogues of SM (SMAs). We report here the effects of the most potent SMase inhibitor, SMA-7, on the LPS-mediated release of tumour necrosis factor-alpha, interleukin-1beta and interleukin-6 from THP-1 macrophages and the pathology of dextran sulphate sodium (DSS)-induced colitis in mice. SMA-7 suppressed the LPS-induced cytokine release and nuclear factor-kappaB activation. LPS stimulation caused a four-fold increase in acid SMase activation, but little increase in neutral SMase activity. The presence of 10 microm SMA-7 caused acid SMase to remain at the control levels and reduced the formation of ceramide. HT-29 cells had significantly decreased cell viability when incubated with media from LPS-stimulated THP-1 macrophages. However, incubating the colon cells in media from both SMA-7 and LPS-treated macrophages caused little decrease in viability, suggesting that ceramide has a role in the LPS-stimulated signalling that releases cytotoxic factors against colon cells. Oral administration of SMA-7 to mice with 2% DSS in the drinking water, for 10 or 21 consecutive days, reduced significantly the cytokine levels in the colon and the severity of colonic injury. These findings suggest a central role for acid SMase/ceramide signalling in the pathology of DSS-induced colitis in mice, indicating a possible preventive or therapeutic role for SMase inhibitor in inflammatory bowel disease.
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Registered trials
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.