Reduction of CXC Chemokine Receptor 3 in anIn VitroModel of Continuous Exposure to Asbestos in a Human T-Cell Line, MT-2

Abstract

Because patients with silicosis who are chronically exposed to silica particles develop not only pulmonary fibrosis, but also complications involving autoimmune diseases such as rheumatoid arthritis and systemic sclerosis, exposure to asbestos may affect the human immune system. This immunologic effect may impair antitumor immune function because cancer complications such as lung cancer and malignant mesothelioma are found in patients exposed to asbestos. To elucidate the antitumor immune status caused by CD4(+) T cells exposed to asbestos, an in vitro T-cell model of long-term and low-level exposure to chrysotile asbestos was established from a human adult T-cell leukemia virus-1-immortalized human polyclonal T cell line, MT-2, and the resulting six sublines showed resistance to asbestos-induced apoptosis after more than 8 months of continuous exposure. The results of DNA microarray analysis showed that the expression of 139 genes was altered by long-term and low-level exposure to asbestos, and the profile was almost similar among the six sublines when compared with the original MT-2 cells that had never been exposed to asbestos. Pathway and network analysis indicated a down-regulation of IFN-γ signaling and expression of CXC chemokine receptor 3 (CXCR3) in the sublines, whereas ELISA and flow cytometry analysis demonstrated a reduction in Th1-related IFN-γ production and cell-surface CXCR3 expression. These findings suggest that chronic exposure to asbestos may reduce antitumor immune status in CD4(+) T cells, and that an in vitro T-cell model may be useful in identifying molecules related to the impairment of antitumor immune function.

Altered functions of alveolar macrophages and NK cells involved in asbestos-related diseases

“…Our findings suggest that these immune-suppressive effects of asbestos exposure might allow early tumor cells to escape from tumor immunity, leading to development of malignant mesothelioma in people exposed to asbestos with mesothelioma showed decreased Th1 cell activity (Fig. 2) [36,37]. The immune system originally plays a role in deletion of exogenous or endogenous nonself substances to maintain health.…”

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

“…The MT-2 cell sub-lines CA1-3, CB1-3 and CR were established after continuous exposure to three kinds of asbestos, namely, chrysotile A, chrysotile B or crocidolite, respectively (Hyodoh et al 2005;Miura et al 2006;Maeda et al 2011Maeda et al , 2012. Those established sub-lines exhibited reduced apoptotic fractions when exposed to CA, CB or CR at a high concentration.…”

“…In our earlier studies, MT-2 -a polyclonal T-cell line immortalized with human adult leukemia virus-1 -was cultured with a low concentration of chrysotile A, chrysotile B or crocidolite for 48 months (Miura et al 2006;Maeda et al 2011Maeda et al , 2012. The resultant seven independent sub-lines were designated CA (chrysotile A) 1-3, CB (chrysotile B) 1-3 and CR (crocidolite).…”

“…Our laboratory has previously performed gene expression analysis of MT-2CA1-3 and of CB1-3 and compared findings against those in parental MT-2 cells (Maeda et al 2011). That analysis revealed that forkhead transcription factor class O1 (FoxO1) was downregulated after long-term exposure of the cells to asbestos.…”

Environmental factors and human health: fibrous and particulate substance-induced immunological disorders and construction of a health-promoting living environment

“…1e) [25,26]. These two molecules were extracted by pathway and network analyses, and IFN-c signaling canonical pathway analysis employing cDNA microarray examination using MT-2 ORG and six independently established continuously exposed sublines (CB1-3 and .…”