Miura Yoshie, Nishimura Yasumitsu, Katsuyama Hironobu, Maeda Megumi, Hayashi Hiroaki, Dong Maolong, Hyodoh Fuminori, Tomita Masafumi, Matsuo Yoshinobu, Uesaka Ayuko, Kuribayashi Kozo, Nakano Takashi, Kishimoto Takumi, Otsuki Takemi
Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 7010192, Japan.
Apoptosis. 2006 Oct;11(10):1825-35. doi: 10.1007/s10495-006-9235-4.
To analyze the possibility that immunological alteration in asbestos-related diseases (ARDs) such as asbestosis (ASB) and malignant mesothelioma (MM) may affect the progression of cancers, a human adult T cell leukemia virus-immortalized T cell line (MT-2Org) was continuously exposed to 10 mug/ml of chrysotile-B (CB), an asbestos. After at least 8 months of exposure, the rate of apoptosis in the cells became very low and the resultant subline was designated MT-2Rst. The MT-2Rst cells were characterized by (i) enhanced expression of bcl-2, with regain of apoptosis-sensitivity by reduction of bcl-2 by siRNA, (ii) excess IL-10 secretion and expression, and (iii) activation of STAT3 that was inhibited by PP2, a specific inhibitor of Src family kinases. These results suggested that the contact between cells and asbestos may affect the human immune system and trigger a cascade of biological events such as activation of Src family kinases, enhancement of IL-10 expression, STAT3 activation and Bcl-2 overexpression. This speculation was partially confirmed by the detection of elevated bcl-2 expression levels in CD4 + peripheral blood T cells from patients with MM compared with those from patients with ASB or healthy donors. Further studies will be required to verify the role of T cells with enhanced bcl-2 expression in tumor progression induced by asbestos exposure.
为了分析诸如石棉肺（ASB）和恶性间皮瘤（MM）等石棉相关疾病（ARDs）中的免疫改变可能影响癌症进展的可能性，将一株人成人T细胞白血病病毒永生化T细胞系（MT-2Org）持续暴露于10微克/毫升的温石棉-B（CB，一种石棉）。暴露至少8个月后，细胞凋亡率变得非常低，所得亚系命名为MT-2Rst。MT-2Rst细胞具有以下特征：（i）bcl-2表达增强，通过小干扰RNA降低bcl-2可恢复凋亡敏感性；（ii）过量分泌和表达IL-10；（iii）STAT3激活，而Src家族激酶的特异性抑制剂PP2可抑制这种激活。这些结果表明，细胞与石棉的接触可能影响人体免疫系统，并引发一系列生物学事件，如Src家族激酶激活、IL-10表达增强、STAT3激活和Bcl-2过表达。与石棉肺患者或健康供体相比，在恶性间皮瘤患者的CD4 +外周血T细胞中检测到bcl-2表达水平升高，这部分证实了上述推测。需要进一步研究来验证bcl-2表达增强的T细胞在石棉暴露诱导的肿瘤进展中的作用。
