Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells

Apoptosis. 2006 Jul 15; [Epub ahead of print] [Link]

Miura Y, Nishimura Y, Katsuyama H, Maeda M, Hayashi H, Dong M, Hyodoh F, Tomita M, Matsuo Y, Uesaka A, Kuribayashi K, Nakano T, Kishimoto T, Otsuki T.

Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama, 7010192, Japan, takemi@med.kawasaki-m.ac.jp.

Abstract

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[Formula: see text] 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.