ArticleJournal of molecular medicine (Berlin, Germany)2015
Acid sphingomyelinase inhibition protects mice from lung edema and lethal Staphylococcus aureus sepsis.
Article in Journal of molecular medicine (Berlin, Germany), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 82 citations in OpenAlex.
- Article
- Association of plasma ceramide with stroke-associated pneumonia in acute ischemic stroke.Frontiers in immunology · 2026Article
- A systematic exploration of gut microbiota-driven blood metabolites in sepsis: an integrated bioinformatics and genetic association study.Frontiers in genetics · 2026Article
- Short-Term Acid Sphingomyelinase Deficiency Exerts Proinflammatory and Antiapoptotic Effects during LPS-induced Lung Injury in Mice.American journal of respiratory cell and molecular biology · 2025Article
- Antibacterial Evaluation of Tricyclic Antidepressants AgainstPathogens (Basel, Switzerland) · 2025Article
- Article
- Forsythoside A inhibited inflammatory response by inhibiting p38 JNK/MAPK/ERK and NF-κB signaling in Staphylococcus aureus pneumonia.Journal of molecular histology · 2025Article
- Could antidepressants increase mood and immunity at the same time?Frontiers in psychiatry · 2025Review
- 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
- Ceramide induces pyroptosis through TXNIP/NLRP3/GSDMD pathway in HUVECs.BMC molecular and cell biology · 2022Article
- Adverse outcomes with extracorporeal adsorbent blood treatments in toxic systemic inflammation: a perspective on possible mechanisms.Annals of intensive care · 2022Review
- Bioactive lipid screening during respiratory tract infections with bacterial and viral pathogens in mice.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- The acid sphingomyelinase/ceramide system in COVID-19.Molecular psychiatry · 2022Review
- The Sphingosine Kinase 2 Inhibitor Opaganib Protects Against Acute Kidney Injury in Mice.International journal of nephrology and renovascular disease · 2022Article
- The Novel Role of Metabolism-Associated Molecular Patterns in Sepsis.Frontiers in cellular and infection microbiology · 2022Review
- Exosome Biogenesis and Lysosome Function Determine Podocyte Exosome Release and Glomerular Inflammatory Response during Hyperhomocysteinemia.The American journal of pathology · 2022Article
- Acid Sphingomyelinase Deficiency: A Clinical and Immunological Perspective.International journal of molecular sciences · 2021Review
- Diagnostic Potential of the Plasma Lipidome in Infectious Disease: Application to Acute SARS-CoV-2 Infection.Metabolites · 2021Article
- Trauma, Metabolomics, Outcomes, and Secrets of the Sphinx.Journal of the American College of Surgeons · 2021Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledPulmonary edema associated with increased vascular permeability is a severe complication of Staphylococcus aureus-induced sepsis and an important cause of human pathology and death. We investigated the role of the mammalian acid sphingomyelinase (Asm)/ceramide system in the development of lung edema caused by S. aureus. Our findings demonstrate that genetic deficiency or pharmacologic inhibition of Asm reduced lung edema in mice infected with S. aureus. The Asm/ceramide system triggered the formation of superoxide, resulting in degradation of tight junction proteins followed by lung edema. Treatment of infected mice with amitriptyline, a potent inhibitor of Asm, protected mice from lung edema caused by S. aureus, but did not reduce systemic bacterial numbers. In turn, treatment with antibiotics reduced bacterial numbers but did not protect mice from lung edema. In contrast, only the combination of antibiotics and amitriptyline inhibited both pulmonary edema and bacteremia protecting mice from lethal sepsis and lung dysfunction suggesting the combination of both drugs as novel treatment option for sepsis. KEY MESSAGES: Antibiotics are often insufficient to cure S. aureus-induced sepsis. S. aureus induces lung edema via the Asm/ceramide system. Genetic deficiency of Asm inhibits lung dysfunction upon infection with S. aureus. Pharmacologic inhibition of Asm reduces lung edema induced by S. aureus. Antibiotics plus amitriptyline protect mice from lung edema and lethal S. aureus sepsis.
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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.