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Science 320 (5876): 674-677

Copyright © 2008 by the American Association for the Advancement of Science

Innate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica

Catherine Dostert,1 Virginie Pétrilli,1 Robin Van Bruggen,2 Chad Steele,3 Brooke T. Mossman,4 Jürg Tschopp1*

Abstract: The inhalation of airborne pollutants, such as asbestos or silica, is linked to inflammation of the lung, fibrosis, and lung cancer. How the presence of pathogenic dust is recognized and how chronic inflammatory diseases are triggered are poorly understood. Here, we show that asbestos and silica are sensed by the Nalp3 inflammasome, whose subsequent activation leads to interleukin-1β secretion. Inflammasome activation is triggered by reactive oxygen species, which are generated by a NADPH oxidase upon particle phagocytosis. (NADPH is the reduced form of nicotinamide adenine dinucleotide phosphate.) In a model of asbestos inhalation, Nalp3–/– mice showed diminished recruitment of inflammatory cells to the lungs, paralleled by lower cytokine production. Our findings implicate the Nalp3 inflammasome in particulate matter–related pulmonary diseases and support its role as a major proinflammatory "danger" receptor.

1 Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland.
2 Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
3 Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, AL 35294, USA.
4 Department of Pathology, University of Vermont College of Medicine, Burlington, VT 05405, USA.

* To whom correspondence should be addressed. E-mail: jurg.tschopp{at}unil.ch


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Induction of Inflammasome-dependent Pyroptosis by Carbon Black Nanoparticles.
A. C. Reisetter, L. V. Stebounova, J. Baltrusaitis, L. Powers, A. Gupta, V. H. Grassian, and M. M. Monick (2011)
J. Biol. Chem. 286, 21844-21852
   Abstract »    Full Text »    PDF »
The Inflammasomes in Kidney Disease.
H.-J. Anders and D. A. Muruve (2011)
J. Am. Soc. Nephrol. 22, 1007-1018
   Abstract »    Full Text »    PDF »
Serum Amyloid A Activates the NLRP3 Inflammasome via P2X7 Receptor and a Cathepsin B-Sensitive Pathway.
K. Niemi, L. Teirila, J. Lappalainen, K. Rajamaki, M. H. Baumann, K. Oorni, H. Wolff, P. T. Kovanen, S. Matikainen, and K. K. Eklund (2011)
J. Immunol. 186, 6119-6128
   Abstract »    Full Text »    PDF »
Varicella-Zoster Virus Infection Triggers Formation of an Interleukin-1{beta} (IL-1{beta})-processing Inflammasome Complex.
A. M. Nour, M. Reichelt, C.-C. Ku, M.-Y. Ho, T. C. Heineman, and A. M. Arvin (2011)
J. Biol. Chem. 286, 17921-17933
   Abstract »    Full Text »    PDF »
The Inflammasome in Atherosclerosis and Type 2 Diabetes.
S. L. Masters, E. Latz, and L. A. J. O'Neill (2011)
Science Translational Medicine 3, 81ps17
   Full Text »    PDF »
Genetic and Molecular Basis of Inflammasome-mediated Disease.
H. M. Hoffman and S. D. Brydges (2011)
J. Biol. Chem. 286, 10889-10896
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Autophagy Controls IL-1{beta} Secretion by Targeting Pro-IL-1{beta} for Degradation.
J. Harris, M. Hartman, C. Roche, S. G. Zeng, A. O'Shea, F. A. Sharp, E. M. Lambe, E. M. Creagh, D. T. Golenbock, J. Tschopp, et al. (2011)
J. Biol. Chem. 286, 9587-9597
   Abstract »    Full Text »    PDF »
Chronic Fine Particulate Matter Exposure Induces Systemic Vascular Dysfunction via NADPH Oxidase and TLR4 Pathways.
T. Kampfrath, A. Maiseyeu, Z. Ying, Z. Shah, J. A. Deiuliis, X. Xu, N. Kherada, R. D. Brook, K. M. Reddy, N. P. Padture, et al. (2011)
Circ. Res. 108, 716-726
   Abstract »    Full Text »    PDF »
Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS).
A. C. Bulua, A. Simon, R. Maddipati, M. Pelletier, H. Park, K.-Y. Kim, M. N. Sack, D. L. Kastner, and R. M. Siegel (2011)
J. Exp. Med. 208, 519-533
   Abstract »    Full Text »    PDF »
Mitochondrial reactive oxygen species drive proinflammatory cytokine production.
E. Naik and V. M. Dixit (2011)
J. Exp. Med. 208, 417-420
   Abstract »    Full Text »    PDF »
Recognition of Cytoplasmic RNA Results in Cathepsin-Dependent Inflammasome Activation and Apoptosis in Human Macrophages.
J. Rintahaka, N. Lietzen, T. Ohman, T. A. Nyman, and S. Matikainen (2011)
J. Immunol. 186, 3085-3092
   Abstract »    Full Text »    PDF »
Meta-Analysis of Genome-Wide Association Studies in >80 000 Subjects Identifies Multiple Loci for C-Reactive Protein Levels.
A. Dehghan, J. Dupuis, M. Barbalic, J. C. Bis, G. Eiriksdottir, C. Lu, N. Pellikka, H. Wallaschofski, J. Kettunen, P. Henneman, et al. (2011)
Circulation 123, 731-738
   Abstract »    Full Text »    PDF »
Inflammasome Activation of Cardiac Fibroblasts Is Essential for Myocardial Ischemia/Reperfusion Injury.
M. Kawaguchi, M. Takahashi, T. Hata, Y. Kashima, F. Usui, H. Morimoto, A. Izawa, Y. Takahashi, J. Masumoto, J. Koyama, et al. (2011)
Circulation 123, 594-604
   Abstract »    Full Text »    PDF »
Divergent Effect of Cobalt and Beryllium Salts on the Fate of Peripheral Blood Monocytes and T Lymphocytes.
F. Paladini, E. Cocco, I. Potolicchio, H. Fazekasova, G. Lombardi, M. T. Fiorillo, and R. Sorrentino (2011)
Toxicol. Sci. 119, 257-269
   Abstract »    Full Text »    PDF »
SR-A/MARCO-mediated ligand delivery enhances intracellular TLR and NLR function, but ligand scavenging from cell surface limits TLR4 response to pathogens.
S. Mukhopadhyay, A. Varin, Y. Chen, B. Liu, K. Tryggvason, and S. Gordon (2011)
Blood 117, 1319-1328
   Abstract »    Full Text »    PDF »

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