Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells.
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.
Miura
Yoshie
Y
Department of Hygiene, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 7010192, Japan.
Nishimura
Yasumitsu
Y
Katsuyama
Hironobu
H
Maeda
Megumi
M
Hayashi
Hiroaki
H
Dong
Maolong
M
Hyodoh
Fuminori
F
Tomita
Masafumi
M
Matsuo
Yoshinobu
Y
Uesaka
Ayuko
A
Kuribayashi
Kozo
K
Nakano
Takashi
T
Kishimoto
Takumi
T
Otsuki
Takemi
T
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001194:Asbestos / Q000009:adverse effects*; D017632:Asbestos, Serpentine / Q000009:adverse effects / Q000494:pharmacology; D001195:Asbestosis / Q000097:blood; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism / Q000502:physiology*; D007962:Leukocytes / Q000473:pathology; D008654:Mesothelioma / Q000097:blood; D008954:Models, Biological; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D017632:Asbestos, Serpentine; D016207:Cytokines; D019253:Proto-Oncogene Proteins c-bcl-2; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051028:bcl-2-Associated X Protein; D016753:Interleukin-10; D001194:Asbestos; D019061:src-Family Kinases