665 Effect of asbestos on foxp3 expression in human t cell line mt-2

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IntroductionAsbestos fibres cause mesothelioma and lung cancer. We propose that asbestos suppress anti-tumour immune system in addition to transformation of mesothelial and lung epithelial cells. It is considered that regulatory T cells, Treg produce inhibitory cytokines to suppress immune reaction against tumour cells. We employed human T cell line MT-2 cell as a model of Treg and cultured them with low concentration of asbestos for 8 months. MT-2 cells exposed with low-concentration asbestos for long term showed higher viability after treatment with high lethal dose of asbestos than original MT-2 cells, and they were designated as MT-2Rst. However, it is still unclear how asbestos induces apoptosis in MT-2 cells and molecular basis of resistance of MT-2Rst cells to high concentration of asbestos. Recently, we found that forkhead transcription factor FoxP3 plays an important role in regulation of apoptosis induced by asbestos.MethodsWe analysed the regulation of FoxP3 transcription in MT-2Org and MT-2Rst cells using luciferase reporter plasmids containing promoter sequence of FoxP3 gene.ResultThere was no significant difference in FoxP3 reporter activity between MT-2Org and MT-2Rst cells.DiscussionOur result indicates that long-term exposure with asbestos suppressed FoxP3 transcription through the epigenetic modification, such as DNA methylation.

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