ArticleToxicology and applied pharmacology2017
Phagolysosome acidification is required for silica and engineered nanoparticle-induced lysosome membrane permeabilization and resultant NLRP3 inflammasome activity.
Article in Toxicology and applied pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 93 citations in OpenAlex.
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- Cinnamaldehyde inhibits the NLRP3 inflammasome and inflammatory response by reducing oxidative stress in Neisseria gonorrhoeae-infected macrophages.Journal of traditional and complementary medicine · 2026Article
- Article
- The Combined Role of Silanols and Oxidative Stress in Determining Engineered Stone Dust Toxicity.ACS organic & inorganic Au · 2026Article
- The interplay between NLRP3 inflammasome and metabolic signals in gouty arthritis.Frontiers in immunology · 2026Review
- 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
- The differential toxicity of three different oxidized nickel compound nanoparticles and the effects of particle surface ligands in mouse alveolar macrophages.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Physico-chemical features and membranolytic activity of dust from low or no crystalline silica engineered stone with implications for toxicological assessment.Scientific reports · 2025Article
- Inflammation-induced lysosomal dysfunction in human iPSC-derived microglia is exacerbated by APOE 4/4 genotype.Journal of neuroinflammation · 2025Article
- The role of NLRP3 inflammasome activation in proinflammatory and cytotoxic effects of metal nanoparticles.Archives of toxicology · 2025Review
- In vitro inflammation and toxicity assessment of pre- and post-incinerated organomodified nanoclays to macrophages using high-throughput screening approaches.Particle and fibre toxicology · 2024Article
- The contribution of pattern recognition receptor signalling in the development of age related macular degeneration: the role of toll-like-receptors and the NLRP3-inflammasome.Journal of neuroinflammation · 2024Review
- Molecular mechanisms underlying NLRP3 inflammasome activation and IL-1β production in air pollution fine particulate matter (PMEnvironmental pollution (Barking, Essex : 1987) · 2024Article
- The role of inflammation in silicosis.Frontiers in pharmacology · 2024Review
- Lysosomal BK channels facilitate silica-induced inflammation in macrophages.Inhalation toxicology · 2024Article
- Ambient atmospheric PM worsens mouse lung injury induced by influenza A virus through lysosomal dysfunction.Respiratory research · 2023Article
- 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
- The role and mechanism of inflammatory response to growing rod implantation in early onset scoliosis.Frontiers in cell and developmental biology · 2023Review
- Cholesterol content regulates silica-induced lysosomal membrane permeability.Frontiers in toxicology · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
NLRP3 inflammasome activation occurs in response to hazardous particle exposures and is critical for the development of particle-induced lung disease. Mechanisms of Lysosome Membrane Permeabilization (LMP), a central pathway for activation of the NLRP3 inflammasome by inhaled particles, are not fully understood. We demonstrate that the lysosomal vATPases inhibitor Bafilomycin A1 blocked LMP in vitro and ex vivo in primary murine macrophages following exposure to silica, multi-walled carbon nanotubes, and titanium nanobelts. Bafilomycin A1 treatment of particle-exposed macrophages also resulted in decreased active cathepsin L in the cytosol, a surrogate measure for leaked cathepsin B, which was associated with less NLRP3 inflammasome activity. Silica-induced LMP was partially dependent upon lysosomal cathepsins B and L, whereas nanoparticle-induced LMP occurred independent of cathepsin activity. Furthermore, inhibition of lysosomal cathepsin activity with CA-074-Me decreased the release of High Mobility Group Box 1. Together, these data support the notion that lysosome acidification is a prerequisite for particle-induced LMP, and the resultant leak of lysosome cathepsins is a primary regulator of ongoing NLRP3 inflammasome activity and release of HMGB1.
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