A1474 Immunotoxicology of Asbestos: Asebstos enhances regulatory T cell function

Monday, March 19, 2012: 16:15
Costa Maya 5 (Cancun Center)

Takemi Otsuki, Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan
Megumi Maeda, Division of Bioscience, Department of Biofunctional Chemistry, Okayama University, Graduate School of Natural Science and Technology, Okayama, Japan
Naoko Kumagai, Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan
Hidenori Matsuzaki, Department of Hygiene, Kawasaki Medical Scool, Kurashiki, Japan
Sehoon Lee, Department of Hygiene, Kawasaki Medical Scool, Kurashiki, Japan
Hiroaki Hayashi, Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan
Handouts
  • A1474 Otsuki T .pdf (451.1 kB)
    • Introduction
    Asbestos-related cancers such as malignant mesothelioma and lung cancer are an important issue in Japan and the world. There are many conflicts concerning economical considerations and medical evidence for these cancers, and much confusion regarding details of the pathological mechanisms of asbestos-induced cancers. For example, there is uncertainty concerning the degree of danger of the iron-absent chrysotile (white) asbestos compared with iron-containing crocidolite (blue) and amosite (brown) asbestos. However, regarding bad prognosis of mesothelioma, medical approaches to ensure recognition of the biological effects of asbestos and the pathological mechanisms of asbestos-induced carcinogenesis, as well as clinical trials to detect the early stage of mesothelioma, should result in better preventions and the cure of asbestos-related malignancies. It is on the basis of these considerations that our group has been investigating the immunological effects of asbestos in relation to reduction of tumor immunity.

    Methods
    A human HTLV-1 immortalized polyclonal T cell line, MT-2, which possesses regulatory T cell function, has been exposed continuously and low-dose of chrysotile, an asbestos, for the establishment of cell line model of asbestos exposure. Continuously exposed subline showed resistance against asbestos-induced apoptosis via contribution of Src-kinase family, upregulation of IL-10, phosphorylation of STAT3, and upregulation of BCL-2. The regulatory function of this subline was compared original (non-exposed) MT-2 line using peripheral blood CD4+ T cells stimulated by anti-CD3 and autologous dendritic cells with CFSE staining.

    Results
    Continuously exposed subline of MT-2 revealed enhanced suppression of responder T cells than that of original MT-2 cells. In addition, soluble factors of regulatory functions such as TGF-beta and IL-10 were produced higher than those of original line.

    Discussion
    Asbestos can enhance reguratory T cell function and this may induce inhibition of tumor immunity. These may affect to the carcinogenesis and progression of cancers caused by asbestos exposure.

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