Differential activation of the inflammasome in THP-1 cells exposed to chrysotile asbestos and Libby “six-mix” amphiboles and subsequent activation of BEAS-2B cells

Li, Muyao; Gunter, Mickey E.; Fukagawa, Naomi K.

doi:10.1016/j.cyto.2012.08.025

Cited by 31 publications

(22 citation statements)

References 53 publications

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“…Comparisons with silica also support the hypothesis that chrysotile does not induce the chronic immune activation/inflammation seen with silica that seems to drive the elevated risk for autoimmune diseases among silica exposed subjects (Otsuki et al, 2007). In addition, an in vitro comparison of the effects of 6-Mix and chrysotile on THP-1 monocytic cells and on epithelial cells showed differences in the overall inflammatory/inflammasome response to these fibers (Li et al, 2012). While each fiber activated the NLRP-3 inflammasome, the response with amphibole appeared to be mediated by reactive oxygen species; the response with chrysotile may have been due to lysozomal rupture.…”

Section: Discussionmentioning

confidence: 99%

Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice

Ferro

Zebedeo

Davis

et al. 2013

Journal of Immunotoxicology

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Exposure to amphibole asbestos has been associated with production of autoantibodies in mice and humans, and increases the risk of systemic autoimmune disease. However, epidemiological studies of chrysotile exposure have not indicated a similar induction of autoimmune responses. To demonstrate this difference in controlled exposures in mice, and to explore possible mechanistic explanations for the difference, C57BL/6 mice were exposed intratracheally to amphibole or chrysotile asbestos, or to saline only. Serum antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), serum cytokines, and immunoglobulin isotypes were evaluated 8 months after the final treatment. The percentages of lymphocyte sub-sets were determined in the spleen and lungs. The results show that amphibole, but not chrysotile, asbestos increases the frequency of ANA/ENA in mice. Amphibole and chrysotile both increased multiple serum cytokines, but only amphibole increased IL-17. Both fibers decreased IgG1, without significant changes in other immunoglobulin isotypes. Although there were no gross changes in overall percentages of T- and B-cells in the spleen or lung, there was a significant increase in the normally rare populations of suppressor B-cells (CD19+, CD5+, CD1d+) in both the spleen and lungs of chrysotile-exposed mice. Overall, the results suggest that, while there may be an inflammatory response to both forms of asbestos, there is an autoimmune response in only the amphibole-exposed, but not the chrysotile-exposed mice. These data have critical implications in terms of screening and health outcomes of asbestos-exposed populations.

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Section: Discussionmentioning

confidence: 99%

Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice

Ferro

Zebedeo

Davis

et al. 2013

Journal of Immunotoxicology

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“…A recent in vitro comparison of the effects of Libby amphibole (6-Mix) and chrysotile on THP-1 monocytic cells and epithelial cells showed differential effects on inflammation/inflammasome activation [72]. Although both fibers activated the NLRP-3 inflammasome, amphibole appeared to do so via reactive oxygen species, while the response with chrysotile may have been mediated through lysosomal rupture.…”

Section: Amphibole Versus Chrysotile: Autoimmunitymentioning

confidence: 99%

“…Despite the appeal of this 2-hit theory to link asbestos pathologies, the literature so far supports association, but not necessarily causation [87, 88]. However, there is the one study recently suggesting differential inflammasome activation by chrysotile and amphibole [72], which supports the idea that a key early trigger involves the inflammasome. This study demonstrated that although caspase cascade, oxidative stress, and the NLRP3 inflammasome were activated by both fibers, there were important differences in the specific pathways that were activated.…”

Section: Targets Of Autoantibodies and Mechanisms Of Diseasementioning

confidence: 99%

“…One hypothesis, therefore, regarding the differences between immune dysfunction with amphibole and chrysotile relates to increased biopersistence of amphibole compared to chrysotile, so that long-term exposure to the fibers leads to accumulation of antigenic cell debris in an inflammatory environment, supporting the development of highly activated APCs that could then trigger autoreactive T and B cells. Alternatively, since both amphibole and chrysotile asbestos can cause oxidative stress and cell death in macrophages and mesothelial cells [91, 92], the mechanism of cell activation and apoptosis may be different [72], leading to different pathways of protein degradation.…”

Section: Targets Of Autoantibodies and Mechanisms Of Diseasementioning

confidence: 99%

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Autoimmunity and Asbestos Exposure

Pfau

Serve

Noonan

2014

Autoimmune Diseases

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Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA), a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a) a lack of statistical power due to relatively small or diffuse exposure cohorts, (b) exposure misclassification, (c) latency of clinical disease, (d) mild or subclinical entities that remain undetected or masked by other pathologies, or (e) effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.

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“…Depending on fiber geometry, some asbestos fibers (such as those that are longer and thinner) penetrate deeper into the lung, and tend to have more deleterious biologic effects (5). The initial, and lasting, assault of asbestos occurs on airway epithelial cells and resident macrophages (6,7), and, because the mechanisms of asbestos-related disease remains unclear, we hypothesize that these epithelial cells and macrophages exposed to asbestos secrete signature factors that contribute to disease development.…”

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confidence: 99%

Exosomes from asbestos‐exposed cells modulate gene expression in mesothelial cells

Munson

Lam²,

Dragon

et al. 2018

FASEB j.

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Asbestos exposure is a determinate cause of many diseases, such as mesothelioma, fibrosis, and lung cancer, and poses a major human health hazard. At this time, there are no identified biomarkers to demarcate asbestos exposure before the presentation of disease and symptoms, and there is only limited understanding of the underlying biology that governs asbestos-induced disease. In our study, we used exosomes, 30-140 nm extracellular vesicles, to gain insight into these knowledge gaps. As inhaled asbestos is first encountered by lung epithelial cells and macrophages, we hypothesize that asbestos-exposed cells secrete exosomes with signature proteomic cargo that can alter the gene expression of mesothelial cells, contributing to disease outcomes like mesothelioma. In the present study using lung epithelial cells (BEAS2B) and macrophages (THP-1), we first show that asbestos exposure causes changes in abundance of some proteins in the exosomes secreted from these cells. Furthermore, exposure of human mesothelial cells (HPM3) to these exosomes resulted in gene expression changes related to epithelial-to-mesenchymal transition and other cancer-related genes. This is the first report to indicate that asbestos-exposed cells secrete exosomes with differentially abundant proteins and that those exosomes have a gene-altering effect on mesothelial cells.-Munson, P., Lam, Y.-W., Dragon, J. MacPherson, M., Shukla, A. Exosomes from asbestos-exposed cells modulate gene expression in mesothelial cells.

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Differential activation of the inflammasome in THP-1 cells exposed to chrysotile asbestos and Libby “six-mix” amphiboles and subsequent activation of BEAS-2B cells

Cited by 31 publications

References 53 publications

Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice

Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice

Autoimmunity and Asbestos Exposure

Exosomes from asbestos‐exposed cells modulate gene expression in mesothelial cells

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