Inhibitory Effects of Anti‐Oxidants on Apoptosis of a Human Polyclonal T‐Cell Line, MT‐2, Induced by an Asbestos, Chrysotile‐A

Abstract

To clarify the effects of silica and silicates on cellular features of lymphocytes, a human T-lymphotropic virus type-1-immortalized polyclonal T-cell line, MT-2, was exposed to various concentrations of chrysotile-A, an asbestos classified as silicate. MT-2 cells underwent apoptosis in a dose-and time-dependent manner. The mitochondrial apoptotic pathway was activated during chrysotile-A-induced apoptosis of MT-2 cells, because of the phosphorylation of JNK and p38, increase of BAX and release of cytochrome-c from mitochondria to cytoplasma. In addition, anti-oxidants such as hydroxyl-radical excluders and capturers of superoxide and inhibitors of superoxide production effectively reduced the size of the apoptotic fraction in MT-2 cells cultured with chrysotile-A. These results indicate that the activation of reactive oxygen species may play a central role in asbestos-induced T-cell apoptosis, and anti-oxidants may help to prevent complications of pneumoconiosis.

Expression of the T Cell Receptor Vβ Repertoire in a Human T Cell Resistant to Asbestos-Induced Apoptosis and Peripheral Blood T Cells from Patients with Silica and Asbestos-Related Diseases

“…We also found that asbestos polyclonally activated CD4-positive T cells and caused activation-induced cell death (5)(6)(7)(8)(9). In addition, PBMCs from healthy donors exposed to asbestos in culture underwent apoptosis (5)(6)(7)(8).…”

“…An HTLV-I-immortalized human polyclonal T cell line, MT-2 (17), was maintained in suspension in RPMI 1640 medium supplemented with 10% fetal bovine serum plus antibodies at 37°C in a humidified atmosphere (9)(10). The UICC (the International Union against Cancer) standard CB sample was kindly provided by the Department of Occupational Health, National Institute for Occupational Health, South Africa (18).…”

“…For this purpose, we employed an HTLV-l-immortalized human polyclonal T cell line, MT-2 (10), for the development of an in vitro model. On short-term and high-level exposure to chrysotile, MT-2 cells underwent apoptosis with the production of ROS via activation ofthe mitochondrial apoptotic pathway with phosphorylation of p38 MAPK and JNK signaling molecules, shifting to a Bax-dominant Bax/Bcl-2 balance, release of cytochrome-c from mitochondria into the cytosol, and activation of caspases 9 and 3 (9). Thereafter, we established a chrysotile-B (CB)-induced apoptosis-resistant subline of MT-2 (MT2Rst), and characterized the differences between the original MT-2 cell line (MT-20rg) and MT-2Rst with regard to the apoptosis-related gene expression, cytokine production and signaling between contact to cells with asbestos fibers and resistance to apoptosis (10).…”

Keynote lecture in the 13th Japanese Society of Immunotoxicology (JSIT 2006)

“…Upon short-term, high-level exposure to chrysotile, MT-2 cells underwent apoptosis with the production of ROS via the activation of the mitochondrial apoptotic pathway with the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun Nterminal kinase (JNK) signaling molecules, resulting in a shiftof the Bax-dominant Bax/Bcl-2 balance, the release of cytochromec from mitochondria into cytosol, and the activation of caspases 9 and 3 as shown on the left side of Fig. 2 and as previously reported (69).…”

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.…”