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Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells
Authors:Yoshie Miura  Yasumitsu Nishimura  Hironobu Katsuyama  Megumi Maeda  Hiroaki Hayashi  Maolong Dong  Fuminori Hyodoh  Masafumi Tomita  Yoshinobu Matsuo  Ayuko Uesaka  Kozo Kuribayashi  Takashi Nakano  Takumi Kishimoto  Takemi Otsuki
Affiliation:(1) Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 7010192, Japan;(2) Department of Public Health, Kawasaki Medical School, Kurashiki, Okayama 7010192, Japan;(3) Department of Medical Toxicology, Kawasaki Medical School, Kurashiki, Okayama 7010192, Japan;(4) Grandsoul Research Institutes for Immunology, Uda, Nara 6332221, Japan;(5) Department of Respiratory Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 6638131, Japan;(6) Okayama Rosai Hospital, Okayama 7028055, Japan
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 μg/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.
Keywords:Asbestos  T cell  IL-10  Bcl-2  Apoptosis
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