**Cytotoxicity Caused by Asbestos Fibers and Acquisition of Resistance by Continuous Exposure in Human T Cells of Resistance by Continuous Exposure in Human T Cells**

**Cytotoxicity Caused by Asbestos Fibers and Acquisition** 

DOI: 10.5772/intechopen.72064

Hidenori Matsuzaki, Suni Lee, Naoko Kumagai-Takei, Yu Min, Nagisa Sada, Kei Yoshitome, Yasumitsu Nishimura, Megumi Maeda and Takemi Otsuki Naoko Kumagai-Takei, Yu Min, Nagisa Sada, Kei Yoshitome, Yasumitsu Nishimura, Megumi Maeda and Takemi Otsuki

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.72064

Hidenori Matsuzaki, Suni Lee,

#### **Abstract**

The cytotoxic effects of asbestos fibers on human T cells and the acquisition of resistance against asbestos-induced apoptosis have been studied. These analyses are based on the establishment of a continuous and relatively low-dose exposure model of human immune cells exposed to asbestos that resembles actual exposure in the human body. The MT-2 T cell line was selected as the candidate for the investigations. A transient and high-dose exposure to chrysotile resulted in apoptosis with production of reactive oxygen species (ROS) and activation of the mitochondrial apoptotic pathway. However, sublines continuously exposed to low dose of asbestos exhibited resistance to asbestosinduced apoptosis. The mechanism of resistance acquisition involved excess production of IL-10, activation of STAT3, and enhanced expression of Bcl-2 located downstream of STAT3. These changes were also found in a subline continuously exposed to crocidolite. Furthermore, sublines showed a marked decrease in the expression of forkhead box O1 (FoxO1) transcription factor. FoxO1 is known to regulate apoptosis and various other cellular processes. Regarding apoptosis, sublines continuously exposed to asbestos showed reduction of FoxP1-driven proapoptotic genes. This pathway is also considered one of the mechanisms that result in resistance to asbestos-induced apoptosis in sublines. These sublines also exhibited several characteristics suggesting reduction of antitumor immunity.

**Keywords:** cytotoxicity, asbestos, T cell, apoptosis, reactive oxygen species, FoxO1, antitumor immunity

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© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons
