Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells
Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells
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DOI：
10.1007/s10495-006-9235-4
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发表时间：
2006-10-01
期刊：
影响因子：
7.2
通讯作者：
Otsuki, Takemi
中科院分区：
文献类型：
--
作者：
Miura, Yoshie;Nishimura, Yasumitsu;Otsuki, Takemi
为了分析石棉相关疾病（ARDs）如石棉沉滞症（ASB）和恶性间皮瘤（MM）中免疫学改变可能影响癌症进展的可能性，将人成人T细胞白血病病毒永生化T细胞系（MT-2 T）连续暴露于10 μ g/ml的温石棉-B（CB），一种石棉。在暴露至少8个月后，细胞中的凋亡率变得非常低，并且所得亚系被命名为MT-2 Rst。MT-2 Rst细胞的特征在于：（i）bcl-2表达增强，通过siRNA减少bcl-2而恢复细胞凋亡敏感性，（ii）IL-10过量分泌和表达，以及（iii）STAT 3的激活，该激活被PP 2（Src家族激酶的特异性抑制剂）抑制。这些结果表明，细胞与石棉的接触可能会影响人体免疫系统，并引发一系列生物学事件，如Src家族激酶的激活，IL-10的表达增强，STAT 3的激活和Bcl-2的过表达。与ASB患者或健康供体相比，MM患者CD 4+外周血T细胞中bcl-2表达水平升高，部分证实了这一推测。需要进一步的研究来验证具有增强的bcl-2表达的T细胞在石棉暴露诱导的肿瘤进展中的作用。
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 mu g/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.