Chronic exposure to asbestos enhances TGF-β1 production in the human adult T cell leukemia virus-immortalized T cell line MT-2

Asbestos exposure causes various tumors such as lung cancer and malignant mesothelioma. To elucidate the immunological alteration in asbestos-related tumors, an asbestos-induced apoptosis-resistant subline (MT-2Rst) was established from a human adult T cell leukemia virusimmortalized T cell line (MT-20rg) by long-term exposure to asbestos chrysotile-B (CB). In this study, transforming growth factor-ßl (TGF-ßl) knockdown using lentiviral vector-mediated RNA interference showed that MT-2Rst cells secreted increased levels of TGF-ßl, and acquired resistance to TGF-ßl-mediated growth inhibition. We showed that exposure of MT-20rg cells to CB activated the mitogenactivated protein kinases (MAPKs), ERK1/2, p38 and JNK1. Furthermore, TGF-ßl-knockdown cells and treatment with MAPK inhibitors revealed that MT-2Rst cells secreted a high level of TGF-ßl mainly through phosphorylation of p38. However, an Annexin V assay indicated that TGF-ßl resistance in MT-2Rst cells was not directly involved in the acquisition of resistance to apoptosis that is triggered by CB exposure. The overall results demonstrate that long-term exposure of MT-20rg cells to CB induces a regulatory T cell-like phenotype, suggesting that chronic exposure to asbestos leads to a state of immune suppression.