Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site VSports app下载. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

. 2008 May 2;320(5876):674-7.
doi: 10.1126/science.1156995. Epub 2008 Apr 10.

"VSports最新版本" Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica

Catherine Dostert  1 , Virginie Pétrilli, Robin Van Bruggen, Chad Steele, Brooke T Mossman, Jürg Tschopp
Affiliations

Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica

Catherine Dostert et al. Science. .

Abstract (V体育安卓版)

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-1beta 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. VSports手机版.

PubMed Disclaimer

VSports - Figures

Fig 1
Fig 1
Asbestos and silica activate IL-1β secretion in human macrophages. (A) THP1 cells were stimulated for 6 h with the indicated amounts (mg/ml media) of asbestos, silica, diesel exhaust particles (DEP), cigarette smoke extract (CSE, in % solution) and MSU. (B) THP1 cells were stimulated with 0.2 mg/ml asbestos, 0.5 mg/ml DEP and 0.2 mg/ml MSU for the indicated times. Media supernatants (SN) were analysed for the presence of mature IL-1β, and cell extracts (Cell) for the presence of proIL-1β by Western blotting. (C) LPS-primed primary human monocyte-derived macrophages (M-CSF) were stimulated for 6 h with asbestos (0.2, 0.1, 0.05 mg/ml), silica (0.5, 0.2, 0.1 mg/ml), DEP (0.2 mg/ml) and MSU (0.2 mg/ml) and analysed by ELISA for IL-1β released into the media. Values are means ± S.E.M.
Fig 2
Fig 2
Asbestos-induced IL-1β secretion is Nalp3 inflammasome-dependent. (A) THP1 cells stably expressing shRNA against the indicated target genes were stimulated for 6 h with 0.2 mg/ml asbestos, 0.2 mg/ml MSU and 3.4 μM nigericin. Media supernatants (SN) and cell extracts (Cell) were analysed by Western blotting as indicated in the text. (B) LPS-primed, murine bone-marrow-derived macrophages (BMDM) from wild-type (WT), Nalp3- or ASC-deficient mice were stimulated for 6 h with the indicated amounts (mg/ml) of asbestos, silica and MSU in the presence of 20 μM zVAD where indicated and analysed for IL-1β secretion and activation of caspase-1 by Western blotting.
Fig 3
Fig 3
Nalp3 inflammasome activation upon asbestos stimulation is dependent on endocytosis and ROS production. (A) THP1 cells were stimulated with the indicated amounts of asbestos or MSU in the presence of 20 μM caspase inhibitor zVAD or 130 mM extracellular KCl. (B) THP1 cells were treated for 6 h with 0.2 mg/ml asbestos, 0.5 mg/ml silica and 0.2 mg/ml MSU. Particles/fibers entering cells are marked with arrows and fibers/particles on cell surface with arrowheads. (C) THP1 cells were stimulated for 6 h with 0.2 mg/ml asbestos, 0.2 mg/ml MSU, 10 μg/ml R837 or 3.4 μM nigericin in the absence or presence of 0.2 μM cytochalasin D. (D) Murine peritoneal macrophages were stimulated with asbestos, MSU or ATP in the presence of N-acetyl-L-cysteine (NAC) (25 mM) or APDC (50 μM). (E) THP1 cells were stimulated with asbestos (0.1 mg/ml) or MSU (0.1 mg/ml) in the presence or absence of deferoxamine mesylate (2 mM) or uricase (0.1 U/ml) respectively. (F) THP1 control cells (mock) or knock-down for the NADPH oxidase subunit p22phox cells were stimulated for 6 h with 0.1 mg/ml asbestos, 0.1 mg/ml MSU or 0.01 mg/ml R837. (G) THP1 control cells (mock) or knock-down for thioredoxin (TRX) cells were stimulated for 6 h with 0.1 mg/ml asbestos, 0.1 mg/ml MSU or 0.5 mg/ml silica. Media supernatants (SN) or cell extracts (Cell) were analysed by Western blotting as indicated in the text.
Fig 4
Fig 4
In vivo inhalation of asbestos results in reduced pulmonary inflammation in Nalp3-deficient mice. (A) Total and (B) differential cell counts in bronchoalveolar lavage fluid (BALF) in 9 day sham- and asbestos-exposed groups. (C) Cytokine/chemokine levels were measured in BALF of 9 day asbestos-exposed mice. Values are means ± S.E.M. *Significantly different from sham of same genotype. †Significantly different from +/+ Asb. (D) A proposed model for asbestos induced inflammasome activation. See text for details.
See this image and copyright information in PMC

"V体育ios版" Comment in

References

    1. Mossman BT, Churg A. Am J Respir Crit Care Med. 1998;157:1666. - PubMed
    1. Ramos-Nino ME, et al. J Cell Biochem. 2006;98:723. - V体育平台登录 - PMC - PubMed
    1. Kamp DW, Weitzman SA. Thorax. 1999;54:638. - PMC - PubMed
    1. Mossman BT, Bignon J, Corn M, Seaton A, Gee JB. Science. 1990;247:294. - PubMed (V体育平台登录)
    1. Rimal B, Greenberg AK, Rom WN. Curr Opin Pulm Med. 2005;11:169. - "VSports app下载" PubMed

Publication types