ArticleParticle and fibre toxicology2017
Imipramine blocks acute silicosis in a mouse model.
Article in Particle and fibre toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 45 citations in OpenAlex.
- Contribution of particle-induced lysosome membrane permeabilization to NLRP3 inflammasome activation and mitochondrial ROS production.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Lysosome dysfunction alters intestinal morphology and lipid metabolism in early neonatal piglets.BMC veterinary research · 2025Article
- Crystalline silica exposure induces multiple systemic autoimmune phenotypes including inflammatory arthritis and nephritis in Collaborative Cross mice with differing sub-clinical autoimmune profiles.bioRxiv : the preprint server for biology · 2025Article
- TMEM175 activity in BK-deficient macrophages maintains lysosomal function and mediates silica-induced inflammatory response in macrophages.Inhalation toxicology · 2025Article
- Imipramine-induced immunomodulation and intracellular growth inhibition duringFrontiers in veterinary science · 2025Article
- Lysosomal BK channels facilitate silica-induced inflammation in macrophages.Inhalation toxicology · 2024Article
- Imipramine Treatment Alters Sphingomyelin, Cholesterol, and Glycerophospholipid Metabolism in Isolated Macrophage Lysosomes.Biomolecules · 2023Article
- Animal models of silicosis: fishing for new therapeutic targets and treatments.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- Cholesterol-dependent molecular mechanisms contribute to cationic amphiphilic drugs' prevention of silica-induced inflammation.European journal of cell biology · 2023Article
- Self-replicating murine ex vivo cultured alveolar macrophages as a model for toxicological studies of particle-induced inflammation.Toxicology and applied pharmacology · 2023Article
- Dasatinib suppresses particulate-induced pyroptosis and acute lung inflammation.Frontiers in pharmacology · 2023Article
- Cholesterol content regulates silica-induced lysosomal membrane permeability.Frontiers in toxicology · 2023Article
- Anti-Fibrotic Effect of Synthetic Noncoding Decoy ODNs for TFEB in an Animal Model of Chronic Kidney Disease.International journal of molecular sciences · 2022Article
- Tetracycline ameliorates silica-induced pulmonary inflammation and fibrosis via inhibition of caspase-1.Respiratory research · 2022Article
- New Insights into Pathomechanisms and Treatment Possibilities for Lung Silicosis.International journal of molecular sciences · 2021Review
- Macrophage fusion caused by particle instillation.Current research in toxicology · 2020Article
- Article
- Omega-3 Docosahexaenoic Acid (DHA) Impedes Silica-Induced Macrophage Corpse Accumulation by Attenuating Cell Death and Potentiating Efferocytosis.Frontiers in immunology · 2020Article
- Mouse pulmonary dose- and time course-responses induced by exposure to nitrogen-doped multi-walled carbon nanotubes.Inhalation toxicology · 2020Article
- Development of experimental silicosis in inbred and outbred mice depends on instillation volume.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundInhalation of crystalline silica is associated with pulmonary inflammation and silicosis. Although silicosis remains a prevalent health problem throughout the world, effective treatment choices are limited. Imipramine (IMP) is a FDA approved tricyclic antidepressant drug with lysosomotropic characteristics. The aim of this study was to evaluate the potential for IMP to reduce silicosis and block phagolysosome membrane permeabilization.
methodsC57BL/6 alveolar macrophages (AM) exposed to crystalline silica ± IMP in vitro were assessed for IL-1β release, cytotoxicity, particle uptake, lysosomal stability, and acid sphingomyelinase activity. Short term (24 h) in vivo studies in mice instilled with silica (± IMP) evaluated inflammation and cytokine release, in addition to cytokine release from ex vivo cultured AM. Long term (six to ten weeks) in vivo studies in mice instilled with silica (± IMP) evaluated histopathology, lung damage, and hydroxyproline content as an indicator of collagen accumulation.
resultsIMP significantly attenuated silica-induced cytotoxicity and release of mature IL-1β from AM in vitro. IMP treatment in vivo reduced silica-induced inflammation in a short-term model. Furthermore, IMP was effective in blocking silica-induced lung damage and collagen deposition in a long-term model. The mechanism by which IMP reduces inflammation was explored by assessing cellular processes such as particle uptake and acid sphingomyelinase activity.
conclusionsTaken together, IMP was anti-inflammatory against silica exposure in vitro and in vivo. The results were consistent with IMP blocking silica-induced phagolysosomal lysis, thereby preventing cell death and IL-1β release. Thus, IMP could be therapeutic for silica-induced inflammation and subsequent disease progression as well as other diseases involving phagolysosomal lysis.
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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.