Asbestos-Induced Cellular and Molecular Alteration of Immunocompetent Cells and Their Relationship with Chronic Inflammation and Carcinogenesis

Matsuzaki, Hidenori; Maeda, Megumi; Lee, Sai Peck; Nishimura, Yasumasa; Kumagai-Τakei, Naoko; Hayashi, Hiroaki; Yamamoto, Shoko; Hatayama, Tamayo; Kojima, Yoshiyuki; Tabata, Rika; Kishimoto, Takumi; Hoshino, Junichi; Otsuki, Takemi

doi:10.1155/2012/492608

Cited by 83 publications

(84 citation statements)

References 70 publications

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“…Coding variants of TNFRSF13B have been implicated in common variable immunodeficiency, and the variant TNFR13BV was found to be up-regulated in both DEW and SP, and the expression was two-fold higher in SP than in DEW ( Table 1). This indicated that TNFR13BV may be involved in the increased and persistent immune response that occurred during silicosis development.It was reported that TNFs, interleukins, interferons, transforming growth factors and chemokines were essential for pulmonary fibrosis, and persistent up-regulation of related cytokines activates fibroblasts, and caused fibrosis of the extracellular matrix (1,13,22,23). In this study TNF, TNF superfamily member 4 isoform X1, interferon beta precursor, IL-6, atypical chemokine receptor 2 and the mutant IL-17F were all up-regulated in DEW and SP (Figures 1,2, Table 1).…”

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confidence: 99%

Proteomic profiling change during the early development of silicosis disease

Miao¹,

Ding²,

Xin³

et al. 2016

J. Thorac. Dis.

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Background: Silicosis is one of several severe occupational diseases for which effective diagnostic tools during early development are currently unavailable. In this study we focused on proteomic profiling during the early stages of silicosis to investigate the pathophysiology and identify the proteins involved.Methods: Two-dimensional (2D) gel electrophoresis and MALDI-TOF-MS were used to assess the proteomic differences between healthy individuals (HI), dust-exposed workers without silicosis (DEW) and silicosis patients (SP). Proteins abundances that differed by a factor of two-fold or greater were subjected to more detailed analysis, and enzyme linked to immunosorbent assay (ELISA) was employed to correlate with protein expression data.Results: Compared with HI, 42 proteins were more abundant and 8 were less abundant in DEW, and these were also differentially accumulated in SP. Closer inspection revealed that serine protease granzyme A, alpha-1-B-glycoprotein (A1BG) and the T4 surface glycoprotein precursor (TSGP) were among the up-regulated proteins in DEW and SP. Significant changes in serine proteases, glycoproteins and protooncogenes may be associated with the response to cytotoxicity and infectious pathogens by activation of T cells, positive regulation of extracellular matrix structural constituents and immune response, and fibroblast proliferation. Up-regulation of cytokines included TNFs, interferon beta precursor, interleukin 6, atypical chemokine receptor 2, TNFR13BV, and mutant IL-17F may be involved in the increased and persistent immune response and fibrosis that occurred during silicosis development.Conclusions: Granzymes, glycoproteins, cytokines and immune factors were dramatically involved in the immune response, metabolism, signal regulation and fibrosis during the early development of silicosis.Proteomic profiling has expanded our understanding of the pathogenesis of silicosis, and identified a number of targets that may be potential biomarkers for early diagnosis of this debilitating disease. J Thorac Dis 2016;8(3):329-341 jtd.amegroups.com extracellular apoptosis related factor (ECM), cytokines and lipid-associated proteins were all reportedly involved in the development of silicosis (3,4). Unfortunately, an effective method involving biomarkers for early diagnosis remained unavailable at present.Significant cellular and molecular alterations ensued following inhalation and deposition of silica minerals in lung tissues (5). Lower-level exposure to silica particles triggered reversible inflammatory lesions, whereas highlevel exposure led to long-term effects on inflammation, cell proliferation, deposition of collagen and extracellular matrix components in mesenchymal cells (1). Alveolar macrophages (AM), neutrophils, T-lymphocytes and mast cells were all involved in fibrogenesis, and cross-talk between these cells played an important role in disease progression. In studies on the interaction of mast cells and neutrophils in mice, animals with intact mast cells endured more severe lung lesi...

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confidence: 99%

Proteomic profiling change during the early development of silicosis disease

Miao¹,

Ding²,

Xin³

et al. 2016

J. Thorac. Dis.

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“…In addition, inactivation of p16/ink4a, inactivation of tumor suppressor PTEN, and somatic mutations of BRCA 1-associated protein-1 (BAP1) were also reported in MPM cells (Kratzke et al 1995;Opitz et al 2008;Bott et al 2011;Testa et al 2011). We have focused on the immunological effects of asbestos; our studies have shown that asbestos fibers suppressed NK and CTL cell functions (Nishimura et al 2009a,b;Matsuzaki et al 2012;Kumagai-Takei et al 2013).…”

Section: Discussionmentioning

confidence: 98%

FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line

Matsuzaki

Lee

Maeda

et al. 2016

Journal of Immunotoxicology

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Asbestos is known to cause malignant mesothelioma and lung cancer. Recent studies implicate tumor immunity in the development of various tumors, including malignant mesothelioma. In order to establish an in vitro T-cell model to clarify the effects of long-term exposure of asbestos on tumor immunity, in this study, human T-cell line MT-2 cells were cultured with asbestos for longer than 8 months and the resultant cells (MT-2Rst) were assessed for the expression of forkhead transcription factor FoxO1. Gene expression analysis revealed that the amount of FoxO1 mRNA decreased after long-term exposure of the MT-2 cells to asbestos. In accordance with this reduction in FoxO1, pro-apoptotic Foxo1 target genes Puma, Fas ligand and Bim were also seen to be downregulated in MT-2Rst cells. Furthermore, shRNA-mediated knock-down of FoxO1 reduced the number of apoptotic parental MT-2 cells after treatment with asbestos. On the other hand, overexpression of FoxO1 did not affect asbestos-induced apoptosis in MT-2Rst cells. These results suggested that FoxO1 played an important role in regulating asbestos-induced apoptosis and confirmed the presence of multiple pathways regulating resistance to asbestos in MT-2Rst cells.ARTICLE HISTORY

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“…Chronic inflammation is believed to play an important role in the etiology of this deadly disease. 4,22 Recently, we found that asbestos can prime and activate the NLRP3 inflammasome in mesothelial cells, 6 resulting in the release of the proinflammatory cytokines IL-1b and IL-18. IL-1b promotes EMT and cancer cell stemness in a number of cell types.…”

Section: Discussionmentioning

confidence: 99%

“…Chronic inflammation has been implicated in the development and progression of MM, 2 and prevalently high circulating cytokines, which are incidentally associated with fibrosis (IL-6, platelet-derived growth factor, and IL-8), have been used as prognosticators of survival for patients with MM. 3,4 A recent massive parallel sequencing study of immortalized and primary mesothelial cells after asbestos exposure found that the most highly up-regulated genes after asbestos exposure belong to inflammatory networks, 5 further implicating inflammation as an important factor in the development of asbestosrelated diseases.…”

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confidence: 99%

Asbestos-Induced Mesothelial to Fibroblastic Transition Is Modulated by the Inflammasome

Thompson

MacPherson

Beuschel

et al. 2017

The American Journal of Pathology

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Despite the causal relationship established between malignant mesothelioma (MM) and asbestos exposure, the exact mechanism by which asbestos induces this neoplasm and other asbestos-related diseases is still not well understood. MM is characterized by chronic inflammation, which is believed to play an intrinsic role in the origin of this disease. We recently found that asbestos activates the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in a protracted manner, leading to an up-regulation of IL-1b and IL-18 production in human mesothelial cells. Combined with biopersistence of asbestos fibers, we hypothesize that this creates an environment of chronic IL-1b signaling in human mesothelial cells, which may promote mesothelial to fibroblastic transition (MFT) in an NLRP3-dependent manner. Using a series of experiments, we found that asbestos induces a fibroblastic transition of mesothelial cells with a gain of mesenchymal markers (vimentin and N-cadherin), whereas epithelial markers, such as E-cadherin, are down-regulated. Use of siRNA against NLRP3, recombinant IL-1b, and IL-1 receptor antagonist confirmed the role of NLRP3 inflammasomeedependent IL-1b in the process. In vivo studies using wild-type and various inflammasome component knockout mice also revealed the process of asbestos-induced mesothelial to fibroblastic transition and its amelioration in caspase-1 knockout mice. Taken together, our data are the first to suggest that asbestos induces mesothelial to fibroblastic transition in an inflammasome-dependent manner. (Am J Pathol 2017, 187: 665e678; http://dx

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Asbestos-Induced Cellular and Molecular Alteration of Immunocompetent Cells and Their Relationship with Chronic Inflammation and Carcinogenesis

Cited by 83 publications

References 70 publications

Proteomic profiling change during the early development of silicosis disease

Proteomic profiling change during the early development of silicosis disease

FoxO1 regulates apoptosis induced by asbestos in the MT-2 human T-cell line

Asbestos-Induced Mesothelial to Fibroblastic Transition Is Modulated by the Inflammasome

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