Proceedings of the National Academy of Sciences - PNAS, 2008-07, Vol.105 (26), p.9035-9040
2008
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- Autor(en) / Beteiligte
- Titel
- Nalp3 inflammasome is essential for the development of silicosis
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2008-07, Vol.105 (26), p.9035-9040
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2008
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Inhalation of crystalline silica and asbestos is known to cause the progressive pulmonary fibrotic disorders silicosis and asbestosis, respectively. Although alveolar macrophages are believed to initiate these inflammatory responses, the mechanism by which this occurs has been unclear. Here we show that the inflammatory response and subsequent development of pulmonary fibrosis after inhalation of silica is dependent on the Nalp3 inflammasome. Stimulation of macrophages with silica results in the activation of caspase-1 in a Nalp3-dependent manner. Macrophages deficient in components of the Nalp3 inflammasome were incapable of secreting the proinflammatory cytokines interleukin (IL)-1β and IL-18 in response to silica. Similarly, asbestos was capable of activating caspase-1 in a Nalp3-dependent manner. Activation of the Nalp3 inflammasome by silica required both an efflux of intracellular potassium and the generation of reactive oxygen species. This study demonstrates a key role for the Nalp3 inflammasome in the pathogenesis of pneumoconiosis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.0803933105Titel-ID: cdi_proquest_miscellaneous_20892848
- Format
- –
- Schlagworte
- Administration, Inhalation, Animals, Apoptosis Regulatory Proteins, Asbestos, Asbestos - administration & dosage, Asbestos - pharmacology, Asbestosis, Biological Sciences, CARD Signaling Adaptor Proteins, Carrier Proteins - metabolism, Collagen - metabolism, Cytochalasins, Cytokines, Cytoskeletal Proteins - deficiency, Cytoskeletal Proteins - immunology, Cytotoxicity, Immunologic - drug effects, Endocytosis - drug effects, Humans, Inflammation, Inflammation - immunology, Inflammatory diseases, Interleukin-1beta - secretion, Interleukin-6 - secretion, Lipopolysaccharides - pharmacology, Lung - drug effects, Lung - immunology, Lung - pathology, Lungs, Macrophages, Macrophages, Peritoneal - drug effects, Macrophages, Peritoneal - secretion, Mice, Mice, Inbred C57BL, NLR Family, Pyrin Domain-Containing 3 Protein, Potassium, Potassium - metabolism, Reactive oxygen species, Reactive Oxygen Species - metabolism, Secretion, Silica, Silicon Dioxide - administration & dosage, Silicon Dioxide - pharmacology, Silicosis, Silicosis - immunology, Silicosis - pathology, Studies, Tumor Necrosis Factor-alpha - secretion