Mouse NLRP3

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

LPS-primed mouse macrophage genetic comparison.

limitations

Priming and activation are separate; dietary silicon is not the particle stimulus. Correction record: A 2026 author correction replaces an erroneously duplicated lower-left Fig. 8c micrograph with the retrieved original. This is a figure correction, not a scientific contradiction or retraction. https://www.nature.com/articles/s41590-026-02468-9

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

The sensor is a distinct necessary component in this model.

primary_references

Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18604214/ · DOI 10.1038/ni.1631

trigger_kind

machinery_impairment Imported condition classification; unverified.

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 440–446

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · LPS-primed mouse macrophage genetic comparison. · source_derived_draft · unverified_draft

## silica-nlrp3-loss The sensor is a distinct necessary component in this model. Nlrp3-deficient macrophages failed to mount the normal silica-induced caspase-1/IL-1 beta response. Model: LPS-primed mouse macrophage genetic comparison. Limitations: Priming and activation are separate; dietary silicon is not the particle stimulus. Correction record: A 2026 author correction replaces an erroneously duplicated lower-left Fig. 8c micrograph with the retrieved original. This is a figure correction, not a scientific contradiction or retraction. https://www.nature.com/articles/s41590-026-02468-9 Evidence access: Primary full text Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18604214/ · DOI 10.1038/ni.1631

evidence_access

Primary full text

experimental_model

Mouse macrophages; 10 micromolar CA-074-Me.

limitations

Pharmacology alone does not establish unique cathepsin B necessity. Correction record: A 2026 author correction replaces an erroneously duplicated lower-left Fig. 8c micrograph with the retrieved original. This is a figure correction, not a scientific contradiction or retraction. https://www.nature.com/articles/s41590-026-02468-9

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A lysosomal protease inhibitor reduced inflammatory output.

primary_references

Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18604214/ · DOI 10.1038/ni.1631

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 448–454

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse macrophages; 10 micromolar CA-074-Me. · source_derived_draft · unverified_draft

## silica-cathepsin-inhibitor A lysosomal protease inhibitor reduced inflammatory output. CA-074-Me reduced silica-triggered IL-1 beta release, supporting a cathepsin-sensitive step. Model: Mouse macrophages; 10 micromolar CA-074-Me. Limitations: Pharmacology alone does not establish unique cathepsin B necessity. Correction record: A 2026 author correction replaces an erroneously duplicated lower-left Fig. 8c micrograph with the retrieved original. This is a figure correction, not a scientific contradiction or retraction. https://www.nature.com/articles/s41590-026-02468-9 Evidence access: Primary full text Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18604214/ · DOI 10.1038/ni.1631

evidence_access

Primary full text

experimental_model

Mouse bone-marrow macrophages with silica/MSU comparisons.

limitations

Compensation and other cathepsins remain possible; no universal dismissal of lysosomal injury.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

Genetic loss did not reproduce the inhibitor-based necessity claim.

primary_references

Activation of NLRP3 inflammasome by crystalline structures via cell surface contact. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25445147/ · DOI 10.1038/srep07281

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 472–478

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse bone-marrow macrophages with silica/MSU comparisons. · source_derived_draft · unverified_draft

## silica-cathepsin-knockout Genetic loss did not reproduce the inhibitor-based necessity claim. Cathepsin-B-deficient macrophages retained crystal-induced IL-1 beta release in this study. Model: Mouse bone-marrow macrophages with silica/MSU comparisons. Limitations: Compensation and other cathepsins remain possible; no universal dismissal of lysosomal injury. Evidence access: Primary full text Activation of NLRP3 inflammasome by crystalline structures via cell surface contact. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25445147/ · DOI 10.1038/srep07281

evidence_access

Primary full text

experimental_model

Pharmacologically altered lysosomal cholesterol handling.

limitations

Not evidence that raising blood cholesterol or dietary cholesterol protects the lung.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

Membrane-lipid handling can modify the response to particles.

primary_references

Role of lysosomes in silica-induced inflammasome activation and inflammation in absence of MARCO. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25054161/ · DOI 10.1155/2014/304180

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 496–502

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pharmacologically altered lysosomal cholesterol handling. · source_derived_draft · unverified_draft

## silica-cholesterol-lysosome Membrane-lipid handling can modify the response to particles. U18666A-induced cholesterol accumulation reduced silica-induced inflammasome activation in mouse alveolar macrophages. Model: Pharmacologically altered lysosomal cholesterol handling. Limitations: Not evidence that raising blood cholesterol or dietary cholesterol protects the lung. Evidence access: Primary full text Role of lysosomes in silica-induced inflammasome activation and inflammation in absence of MARCO. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25054161/ · DOI 10.1155/2014/304180

evidence_access

Primary full text

experimental_model

Mouse RAW-ASC cells; 1 microgram/mL leupeptin.

limitations

Leupeptin is not cathepsin-B-specific; measured abundance is not a selective genetic activity test.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A protease-inhibitor result also failed to establish cathepsin B necessity.

primary_references

Characterization of Cathepsin B in Mediating Silica Nanoparticle-Induced Macrophage Pyroptosis via an NLRP3-Dependent Manner. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35966002/ · DOI 10.2147/JIR.S371536

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 512–518

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse RAW-ASC cells; 1 microgram/mL leupeptin. · source_derived_draft · unverified_draft

## silica-leupeptin-null A protease-inhibitor result also failed to establish cathepsin B necessity. Leupeptin reduced the measured cathepsin-B signal without preventing the nanoparticle-associated pyroptosis response. Model: Mouse RAW-ASC cells; 1 microgram/mL leupeptin. Limitations: Leupeptin is not cathepsin-B-specific; measured abundance is not a selective genetic activity test. Evidence access: Primary full text Characterization of Cathepsin B in Mediating Silica Nanoparticle-Induced Macrophage Pyroptosis via an NLRP3-Dependent Manner. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35966002/ · DOI 10.2147/JIR.S371536

evidence_access

Primary full text

experimental_model

Mouse RAW-ASC cells; LPS priming, 100 micrograms/mL silica, approximately 30 nm particles.

limitations

Do not assume all sizes, coatings or amorphous preparations behave identically.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

A nanoparticle preparation was examined separately from quartz.

primary_references

Characterization of Cathepsin B in Mediating Silica Nanoparticle-Induced Macrophage Pyroptosis via an NLRP3-Dependent Manner. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35966002/ · DOI 10.2147/JIR.S371536

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 504–510

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse RAW-ASC cells; LPS priming, 100 micrograms/mL silica, approximately 30 nm particles. · source_derived_draft · unverified_draft

## silica-nanoparticle-nlrp3 A nanoparticle preparation was examined separately from quartz. Silica nanoparticles increased inflammasome/pyroptosis-associated markers; MCC950 suppressed the response. Model: Mouse RAW-ASC cells; LPS priming, 100 micrograms/mL silica, approximately 30 nm particles. Limitations: Do not assume all sizes, coatings or amorphous preparations behave identically. Evidence access: Primary full text Characterization of Cathepsin B in Mediating Silica Nanoparticle-Induced Macrophage Pyroptosis via an NLRP3-Dependent Manner. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35966002/ · DOI 10.2147/JIR.S371536

evidence_access

Primary full text

experimental_model

Mouse macrophage genetic comparison.

limitations

Does not exclude every ROS source or establish NADPH depletion. Correction record: A 2026 author correction replaces an erroneously duplicated lower-left Fig. 8c micrograph with the retrieved original. This is a figure correction, not a scientific contradiction or retraction. https://www.nature.com/articles/s41590-026-02468-9

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

The phagocyte NADPH oxidase burst was not obligatory in this model.

primary_references

Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18604214/ · DOI 10.1038/ni.1631

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 456–462

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse macrophage genetic comparison. · source_derived_draft · unverified_draft

## silica-nox2-null The phagocyte NADPH oxidase burst was not obligatory in this model. Cybb/gp91phox-deficient macrophages retained silica-triggered inflammasome responses. Model: Mouse macrophage genetic comparison. Limitations: Does not exclude every ROS source or establish NADPH depletion. Correction record: A 2026 author correction replaces an erroneously duplicated lower-left Fig. 8c micrograph with the retrieved original. This is a figure correction, not a scientific contradiction or retraction. https://www.nature.com/articles/s41590-026-02468-9 Evidence access: Primary full text Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18604214/ · DOI 10.1038/ni.1631

evidence_access

Primary full text

experimental_model

Mouse macrophages; 130 mM KCl experimental condition.

limitations

Not a potassium supplement treatment; no specific channel identity was established.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

The potassium gradient gates this inflammatory response.

primary_references

Activation of NLRP3 inflammasome by crystalline structures via cell surface contact. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25445147/ · DOI 10.1038/srep07281

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 480–486

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse macrophages; 130 mM KCl experimental condition. · source_derived_draft · unverified_draft

## silica-potassium-gate The potassium gradient gates this inflammatory response. High extracellular potassium blocked silica-induced caspase-1 processing and IL-1 beta release, including during low-dose uptake blockade. Model: Mouse macrophages; 130 mM KCl experimental condition. Limitations: Not a potassium supplement treatment; no specific channel identity was established. Evidence access: Primary full text Activation of NLRP3 inflammasome by crystalline structures via cell surface contact. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25445147/ · DOI 10.1038/srep07281

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse macrophages; related human PBMC result separately reported in the paper.

limitations

Inhibitor dose and non-uptake effects require comparison with later low-dose experiments. Correction record: A 2026 author correction replaces an erroneously duplicated lower-left Fig. 8c micrograph with the retrieved original. This is a figure correction, not a scientific contradiction or retraction. https://www.nature.com/articles/s41590-026-02468-9

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

Blocking engulfment also blocked inflammatory output in this experiment.

primary_references

Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18604214/ · DOI 10.1038/ni.1631

trigger_kind

machinery_impairment Imported condition classification; unverified.

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 432–438

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse macrophages; related human PBMC result separately reported in the paper. · source_derived_draft · unverified_draft

## silica-uptake-block-2008 Blocking engulfment also blocked inflammatory output in this experiment. Cytochalasin D blocked silica uptake and IL-1 beta release, supporting a phagocytosis-dependent interpretation. Model: Mouse macrophages; related human PBMC result separately reported in the paper. Limitations: Inhibitor dose and non-uptake effects require comparison with later low-dose experiments. Correction record: A 2026 author correction replaces an erroneously duplicated lower-left Fig. 8c micrograph with the retrieved original. This is a figure correction, not a scientific contradiction or retraction. https://www.nature.com/articles/s41590-026-02468-9 Evidence access: Primary full text Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18604214/ · DOI 10.1038/ni.1631

evidence_access

Primary full text

experimental_model

Mouse bone-marrow macrophages; 0.25–0.5 micromolar cytochalasin D.

limitations

Immobilized epoxy-crystal experiments used MSU, not silica; do not transfer that detail between materials.

nutrient_topic

Silica collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Silica and soluble silicon

plain_language

Surface-associated crystals could still trigger a response when uptake was blocked.

primary_references

Activation of NLRP3 inflammasome by crystalline structures via cell surface contact. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25445147/ · DOI 10.1038/srep07281

Silica: soluble silicon, cellular transport and particle-specific mechanisms (2026-09-19) · lines 464–470

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse bone-marrow macrophages; 0.25–0.5 micromolar cytochalasin D. · source_derived_draft · unverified_draft

## silica-uptake-block-2014 Surface-associated crystals could still trigger a response when uptake was blocked. Low-dose cytochalasin D blocked silica engulfment while preserving caspase-1 processing and IL-1 beta release. Model: Mouse bone-marrow macrophages; 0.25–0.5 micromolar cytochalasin D. Limitations: Immobilized epoxy-crystal experiments used MSU, not silica; do not transfer that detail between materials. Evidence access: Primary full text Activation of NLRP3 inflammasome by crystalline structures via cell surface contact. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25445147/ · DOI 10.1038/srep07281

dose

Naringenin 100 mg/kg/day by gavage in the mouse arm

duration

7 days in mice

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

evidence_scope

literature_reviewed; model-specific source-derived curation

experimental_model

Wild-type and NLRP3-knockout mice; HepG2 cells, hepatocytes and Kupffer cells

limitations

The methionine/choline-deficient model and high dose do not reproduce ordinary citrus intake or all human NAFLD.

nutrient_topic

Naringenin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Naringenin

organism

Wild-type and NLRP3-knockout mice; HepG2 cells, hepatocytes and Kupffer cells

plain_language

Naringenin reduced lipid accumulation and inflammatory signaling in methionine/choline-deficient mice and cells; effects were lost in NLRP3-null hepatocytes and restored after NLRP3 re-expression.

primary_references

Naringenin attenuates non-alcoholic fatty liver disease by down-regulating the NLRP3/NF-κB pathway in mice. (2020). https://pubmed.ncbi.nlm.nih.gov/31758699/ DOI: 10.1111/bph.14938

route

Oral and in vitro

tissue

NAFLD lipid accumulation and NLRP3/NF-kappaB signaling

Naringenin: mechanism of action and interactions (2026-09-20) · lines 121–130

Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · Wild-type and NLRP3-knockout mice; HepG2 cells, hepatocytes and Kupffer cells · source_derived_draft · unverified_draft

## naringenin-nlrp3-dependence Naringenin reduced lipid accumulation and inflammatory signaling in methionine/choline-deficient mice and cells; effects were lost in NLRP3-null hepatocytes and restored after NLRP3 re-expression. Model/species: Wild-type and NLRP3-knockout mice; HepG2 cells, hepatocytes and Kupffer cells Tissue/system: NAFLD lipid accumulation and NLRP3/NF-kappaB signaling Exposure: Naringenin 100 mg/kg/day by gavage in the mouse arm Route: Oral and in vitro Duration: 7 days in mice Limits: The methionine/choline-deficient model and high dose do not reproduce ordinary citrus intake or all human NAFLD. Primary reference: Naringenin attenuates non-alcoholic fatty liver disease by down-regulating the NLRP3/NF-κB pathway in mice. (2020). https://pubmed.ncbi.nlm.nih.gov/31758699/ DOI: 10.1111/bph.14938 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.