Silica-induced NLRP3 inflammasome activation in vitro and in rat lungs

Autor: Wolfgang Drommer, Catrin Albrecht, Paul Borm, Irene M. J. Eurlings, Niki L. Reynaert, Roel P. F. Schins, Timothy N. Perkins, Paul Peeters, Emiel F.M. Wouters
Přispěvatelé: Pulmonologie, RS: CAPHRI School for Public Health and Primary Care, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, RS: CAPHRI - Asthma and COPD
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Pathology
Inflammasomes
Health
Toxicology and Mutagenesis
Toxicology
chemistry.chemical_compound
TRX
IL-1 beta
FIBROSIS
SURFACE REACTIVITY
Toxicity Tests
Chronic
Lung
HMGB1
Air Pollutants
Inhalation Exposure
medicine.diagnostic_test
biology
Caspase 1
PVNO
Inflammasome
EPITHELIAL-CELLS
General Medicine
NALP3 INFLAMMASOME
respiratory system
Silicon Dioxide
IL-1β
Caspase-1
QUARTZ
Female
medicine.symptom
medicine.drug
AMORPHOUS SILICA
medicine.medical_specialty
Materials science
Cell Survival
Surface Properties
Silicosis
COAL-WORKERS PNEUMOCONIOSIS
Inflammation
Bronchi
Respiratory Mucosa
Cell Line
Western blot
PULMONARY INFLAMMATION
ASBESTOS
NLR Family
Pyrin Domain-Containing 3 Protein
medicine
Toxicity Tests
Acute
Animals
Humans
Particle Size
Rats
Wistar
Sirius Red
Research
Macrophages
medicine.disease
Molecular biology
NLRP3 inflammasome
Crystalline silica
Rats
chemistry
DNA-DAMAGE
bFGF
Cell culture
biology.protein
Carrier Proteins
Biomarkers
Zdroj: Particle and Fibre Toxicology
Particle and Fibre Toxicology, 11(1):58. BioMed Central Ltd
ISSN: 1743-8977
Popis: Rationale Mineral particles in the lung cause inflammation and silicosis. In myeloid and bronchial epithelial cells the inflammasome plays a role in responses to crystalline silica. Thioredoxin (TRX) and its inhibitory protein TRX-interacting protein link oxidative stress with inflammasome activation. We investigated inflammasome activation by crystalline silica polymorphs and modulation by TRX in vitro, as well as its localization and the importance of silica surface reactivity in rats. Methods We exposed bronchial epithelial cells and differentiated macrophages to silica polymorphs quartz and cristobalite and measured caspase-1 activity as well as the release of IL-1β, bFGF and HMGB1; including after TRX overexpression or treatment with recombinant TRX. Rats were intratracheally instilled with vehicle control, Dörentruper quartz (DQ12) or DQ12 coated with polyvinylpyridine N-oxide. At days 3, 7, 28, 90, 180 and 360 five animals per treatment group were sacrificed. Hallmarks of silicosis were assessed with Haematoxylin-eosin and Sirius Red stainings. Caspase-1 activity in the bronchoalveolar lavage and caspase-1 and IL-1β localization in lung tissue were determined using Western blot and immunohistochemistry (IHC). Results Silica polymorphs triggered secretion of IL-1β, bFGF and HMGB1 in a surface reactivity dependent manner. Inflammasome readouts linked with caspase-1 enzymatic activity were attenuated by TRX overexpression or treatment. At day 3 and 7 increased caspase-1 activity was detected in BALF of the DQ12 group and increased levels of caspase-1 and IL-1β were observed with IHC in the DQ12 group compared to controls. DQ12 exposure revealed silicotic nodules at 180 and 360 days. Particle surface modification markedly attenuated the grade of inflammation and lymphocyte influx and attenuated the level of inflammasome activation, indicating that the development of silicosis and inflammasome activation is determined by crystalline silica surface reactivity. Conclusion Our novel data indicate the pivotal role of surface reactivity of crystalline silica to activate the inflammasome in cultures of both epithelial cells and macrophages. Inhibitory capacity of the antioxidant TRX to inflammasome activation was evidenced. DQ12 quartz exposure induced acute and chronic functional activation of the inflammasome in the heterogeneous cell populations of the lung in associated with its crystalline surface reactivity. Electronic supplementary material The online version of this article (doi:10.1186/s12989-014-0058-0) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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