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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Moosman BT, Bignon J, Corn M, Seatona A, Gee JBL (1990) Asbestos: scientific developments and implications for public policy. Science 247:294–301
Moosman BT, Churg A (1998) State-of-the-art: mechanisms in the pathogenesis of asbestosis and silicosis. Am J Respir Crit Care Med 157:1666–1680
Robinson BW, Musk AW, Lake RA (2005) Malignant mesothelioma. Lancet 366:397–408
Sterman DH, Albelda SM (2005) Advances in the diagnosis, evaluation, and management of malignant pleural mesothelioma. Respirology 10:266–283
Hughes RS (2005) Malignant pleural mesothelioma. Am J Med Sci 329:29–44
http://www-cie.iarc.fr/htdocs/monographs/vol68/silica.htm
Upadhyay D, Kamp DW (2003) Asbestos-induced pulmonary toxicity: role of DNA damage and apoptosis. Exp Biol Med (Maywood) 228:650–659
Shukla A, Ramos-Nino M, Mossman B (2003) Cell signaling and transcription factor activation by asbestos in lung injury and disease. Int J Biochem Cell Biol 35:1198–1209
Shukla A, Gulumian M, Hei TK, Kamp D, Rahman Q, Mossman BT (2003) Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases. Free Radic Biol Med 34:1117–1129
Kamp DW, Panduri V, Weitzman SA, Chandel N (2002) Asbestos-induced alveolar epithelial cell apoptosis: role of mitochondrial dysfunction caused by iron-derived free radicals. Mol Cell Biochem 234–235:153–160
Panduri V, Weitzman SA, Chandel NS, Kamp DW (2003) The mitochondria-regulated death pathway mediates asbestos-induced alveolar epithelial cell apoptosis. Am J Respir Cell Mol Biol 28:241–248
Panduri V, Weitzman SA, Chandel N, Kamp DW (2004) Mitochondrial-derived free radicals mediate asbestos-induced alveolar epithelial cell apoptosis. Am J Physiol Lung Cell Mol Physiol 286:L1220–L11227
Song L, Turkson J, Karrs JG, Jove R, Haura EB (2003) Activation of Stat3 by receptor tyrosine kinases and cytokines regulates survival in human non-small cell carcinoma cells. Oncogene 22:4150–4165
Vega MI, Huerta-Yepaz S, Garban H, Jazirehi A, Emmanouilides C, Bonavida B (2004) Rituximab inhibits p38 MAPK activity in 2F7 B NHL and decreases IL-10 transcription: pivotal role of p38 MAPK in drug resistance. Oncogene 23:3530–3540
Aikoh T, Tomokuni A, Matsuki T, Hyodoh F, Ueki H, Otsuki T, Ueki A (1998) Activation-induced cell death in human peripheral bood lymphocytes after stimulation with silicatein vitro. Int J Oncol 12:1355–1359
Ma Z, Otsuki T, Tomokuni A, Aikoh T, Matsuki T, Sakaguchi H, Isozaki Y, Hyodoh F, Uehira K, Isoda K, Ueki A (1999) Man-made mineral fibers induce apoptosis of human peripheral blood mononuclear cells similarly to chrysotile B. Int J Mol Med 4:633–637
Ueki A, Yamaguchi M, Ueki H, Watanabe Y, Ohsawa G, Kinugawa K, Kawakami Y, Hyodoh F (1994) Polychlonal human T-cell activation by silicatein vitro. Immunology 82:332–335
Hyodoh F, Takata-Tomokuni A, Miura Y, Sakaguchi H, Hatayama T, Hatada S, Katsuyama H, Matsuo Y, Otsuki T (2005) Inhibitory effects of anti-oxidants on apoptosis of a human polyclonal T-cell line, MT-2, induced by an asbestos, chrysotile-A. Scan J Immunol 61:442–448
Miyoshi I, Kubonishi I, Yoshimoto S (1981) Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukemic T cells. Nature 294:770–771
Otsuki T, Hata H, Harada N, Matsuzaki H, Yata K, Wada H, Yawata Y. Ueki A, Yamada O (2000) Cellular biological differences between KMS-12-PE and KMS-12-BM human myeloma cell lines, which were established from a single patient. Int J Hematol 72:216–222
Otsuki T, Yata K, Takata-Tomokuni A, Hyodoh F, Miura Y, Sakaguchi H, Hatayama T, Hatada S, Tsujioka T, Sato Y, Murakami H, Sadahira Y, Sugihara T (2004) Expression of PGP9.5 (Protein Gene Product 9.5)/UCHL-1 (Ubiquitin-C-terminal hydrolase 1) in human myeloma cells. Br J Haematol 127:292–298
Miura Y, Murata Y, Utsumi K, Takahata K, Tada M, Otsuki T (2005) The inhibitory effect of dibutyryl cyclicAMP on docosahexaenoic acid-induced apoptosis involves phosphatidylinositol-3 kinase pathway in HL-60 cells. Environ Health Prev Med 10:184–189
Takata-Tomokuni A, Ueki A, Shiwa M, Isozaki Y, Hatayama T, Katsuyama H, Hyodoh F, Fujimoto W, Ueki H, Kusaka M, Arikuni H, Otsuki T (2005) Detection, epitope-mapping, and function of anti-Fas autoantibody in patients with silicosis. Immunology 116:221–229
Otsuki T, Yamada O, Kurebayashi J, Moriya T, Sakaguchi H, Kunisue H, Yata K, Uno M, Yawata Y, Ueki A (2000) Estrogen receptors in human myeloma cells. Cancer Res 60:1434–1441
Otsuki T, Yata K, Sakaguchi H, Kurebayashi J, Matsuo Y, Uno M, Fujii T, Eda S, Isozaki Y, Yawata Y, Yamada O, Wada H, Sugihara T, Ueki A (2002) IL-10 abolishes the growth inhibitory effects of all trans retinoic acid (ATRA) on human myeloma cells. Br J Haematol 116:787–795
Battle TE, Frank DA (2002) The role of STATs in apoptosis. Curr Mol Med 2:381–392
Steinman RA, Wentzel A, Lu Y, Stehle C, Grandis JR (2003) Activation of Stat3 by cell confluence reveals negative regulation of Stat3 by cdk2. Oncogene 22:3608–3615
Gao H, Guo RF, Speyer CL, Reuben J, Neff TA, Hoesel LM, Riedemann NC, McClintock SD, Sarma JV, Van Rooijen N, Zetoune FS, Ward PA (2004) Stat3 activation in acute lung injury. J Immunol 172:7703–7712
Alas S, Bonavida B (2001) Rituximab inactivates signal transducer and activation of transcription 3 (STAT3) activity in B-non-Hodgkin’s lymphoma through inhibition of the interleukin 10 autocrine/paracrine loop and results in down-regulation of Bcl-2 and sensitization to cytotoxic drugs. Cancer Res 61:5137–5144
Alas S, Emmanouilides C, Bonavida B (2001) Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin’s lymphoma to apoptosis. Clin. Cancer Res 7:709–723
Tomokuni A, Aikoh T, Matsuki T, Isozaki Y, Otsuki T, Kita S, Ueki H, Kusaka M, Kishimoto T, Ueki A (1997) Elevation soluble Fas/APO-1 (CD95) levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumors. Clin Exp Immunol 110:303–309
Otsuki T, Sakaguchi H, Tomokuni A, Aikoh T, Matsuki T, Kawakami Y, Kusaka M, Ueki H, Kita S, Ueki A (1998) Soluble Fas mRNA is dominantly expressed in cases with silicosis. Immunology 94:258–262
Otsuki T, Tomokuni A, Sakaguchi H, Aikoh T, Matsuki T, Isozaki Y, Hyodoh F, Ueki H, Kusaka M, Kita S, Ueki A (2000) Over-expression of the decoy receptor 3 (DcR3) gene in peripheral blood mononuclear cells (PBMC) derived from silicosis patients. Clin Exp Immunol 119:323–327
Ueki A, Isozaki Y, Tomokuni A, Hatayama T, Ueki H, Kusaka M (2002) Intermolecular epitope spreading among anti-caspase-8 autoantibodies in patients with silicosis, systemic sclerosis and systemic lupus erythematosus, as well as in healthy individuals. Clin Exp Immunol 129:556–561
Ueki A, Isozaki Y, Tomokuni A, Ueki H, Kusaka M, Tanaka S, Otsuki T, Sakaguchi H, Hyodoh F (2005) Different distribution of HLA class II alleles in anti-topoisomerase I autoantibody responders between silicosis and systemic sclerosis patients, with a common distinct amino acid sequence in the HLA-DQB1 domain. Immunobiology 204:458–465
Ueki H, Kohda M, Nobutoh T, Yamaguchi M, Omori K, Miyashita Y, Hashimoto T, Komai A, Tomokuni A, Ueki A (2001) Antidesmoglein autoantibodies in silicosis patients with no bullous diseases. Dermatology 202:16–21
Nomura T, Sakaguchi S (2005) Naturally arising CD25 +CD4 + regulatory T cells in tumor immunity. Curr Top Microbiol Immunol 293:287–302
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Miura, Y., Nishimura, Y., Katsuyama, H. et al. Involvement of IL-10 and Bcl-2 in resistance against an asbestos-induced apoptosis of T cells. Apoptosis 11, 1825–1835 (2006). https://doi.org/10.1007/s10495-006-9235-4
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10495-006-9235-4