Immunological effects of silica and asbestosis. Cell Mol Immunol 4:261-268

Department of Hygiene, Kawasaki Medical School, Matsushima 577, Kurashiki 7010192, Japan.
Cellular & molecular immunology (Impact Factor: 4.11). 09/2007; 4(4):261-8.
Source: PubMed


Silicosis patients (SILs) and patients who have been exposed to asbestos develop not only respiratory diseases but also certain immunological disorders. In particular, SIL sometimes complicates autoimmune diseases such as systemic scleroderma, rheumatoid arthritis (known as Caplan syndrome), and systemic lupus erythematoses. In addition, malignant complications such as lung cancer and malignant mesothelioma often occur in patients exposed to asbestos, and may be involved in the reduction of tumor immunity. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica, more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors, respectively. In addition, immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cell-mediated therapies, various cytokines, and molecule-targeting therapies. In particular, as the incidence of asbestos-related malignancies is increasing and such malignancies have been a medical and social problem since the summer of 2005 in Japan, efforts should be focused on developing a cure for these diseases to eliminate nationwide anxiety.

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Available from: Shuko Murakami, Jun 23, 2014
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    • "In addition, there is evidence that chrysotile may induce long-term immunosuppressive effects among lymphocytes subsets of mesothelioma patients, leading to susceptibility to cancer but not autoimmune responses [35, 69, 70]. Comparisons with silica 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 [70]. This hypothesis is also supported by the work by a Japanese group [30, 71] that has shown immunosuppression in chrysotile exposed cells in vitro and ex vivo. "
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    ABSTRACT: 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.
    Full-text · Article · Apr 2014
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    • "Examples include exposures such as smoking or occupational exposure to silica dust. Smoking, for example, may contribute to an ongoing cycle of inflammation and self-reactivity initiated by citrullination [15], while silica effects may persist due to the body's inability to destroy or clear silica from the lung, associated lymph nodes, or other organs [16]. Literature on the role of ongoing exposures and associated autoimmune diseases is not well developed, but in many cases it seems reasonable for patients and clinicians to explore whether exposures can be avoided or reduced to ameliorate symptoms and prevent exacerbations. "
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    ABSTRACT: Increasing evidence supports a role for the environment in the development of autoimmune diseases, as reviewed in the accompanying three papers from the National Institute of Environmental Health Sciences Expert Panel Workshop. An important unresolved issue, however, is the development of criteria for identifying autoimmune disease phenotypes for which the environment plays a causative role, herein referred to as environmentally associated autoimmune diseases. There are several different areas in which such criteria need to be developed, including: 1) identifying the necessary and sufficient data to define environmental risk factors for autoimmune diseases meeting current classification criteria; 2) establishing the existence of and criteria for new environmentally associated autoimmune disorders that do not meet current disease classification criteria; and 3) identifying in clinical practice specific environmental agents that induce autoimmune disease in individual patients. Here we discuss approaches that could be useful for developing criteria in these three areas, as well as factors that should be considered in evaluating the evidence for criteria that can distinguish individuals with such disorders from individuals without such disorders with high sensitivity and specificity. Current studies suggest that multiple lines of complementary evidence will be important and that in many cases there will be clinical, serologic, genetic, epigenetic, and/or other laboratory features that could be incorporated as criteria for environmentally associated autoimmune diseases to improve diagnosis and treatment and possibly allow for preventative strategies in the future.
    Full-text · Article · Jul 2012 · Journal of Autoimmunity
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    • "Overall findings indicated that the low-dose and continuous exposure of the human T cell line MT-2 to crocidolite resulted in characteristics that resembled those of the subline exposed to chrysotile, even though there are physical and chemical differences between these two types of asbestos. Further investigations will provide a clinical background to clarify the effects of asbestos fibers on tumor immunity in asbestos-exposed individuals (Maeda et al., 2010; Otsuki et al., 2007). This research may lead to the development of early detection tools such as plasma markers for exposure to asbestos or the detection of asbestos-induced tumors, as well as the chemical prevention of these tumors by modifying the immunological status of the asbestos-exposed population. "
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    ABSTRACT: We have been investigating the immunological effects of asbestos. The establishment of a low-dose and continuously exposed human T cell line, HTLV-1 immortalized MT-2, to chrysotile (CB) revealed reduction of CXCR3 chemokine receptor and production of IFN-γ that caused a decline of tumor immunity. These effects were coupled with upregulation of IL-10, TGF-β, and BCL-2 in asbestos-exposed patients. To observe the immunological effects of crocidolite (CR) on human T cells, a trial to establish a low-dose and continuously exposed model was conducted and compared with a previously reported CB-exposed model (MT-2CB). Transient exposure of MT-2 original cells to CB or CR induced a similar level of apoptosis and growth inhibition. The establishment of a continuously exposed subline to CR (MT-2CR) revealed resistance against CR-induced apoptosis and upregulation of the BCL-2/BAX ratio similar to that recorded for MT-2CB. Both sublines showed reduced production of IFN-γ, TNF-α, and IL-6 with increased IL-10. cDNA microarray with network/pathway analyses focusing on transcription factors revealed that many similar factors related to cell proliferation were involved following continuous exposure to asbestos in both MT-2CB and MT-2CR. These results indicate that both CB and CR fibers affect human T cells with similar degrees even though the carcinogenic activity of these substances differs due to their chemical and physical forms. Trials to identify early detection markers for asbestos exposure or the occurrence of asbestos-inducing malignancies using these findings may lead to the development of clinical tools for asbestos-related diseases and chemoprevention that modifies the reduced tumor immunity.
    Full-text · Article · May 2012 · Science of The Total Environment
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