RESUMEN
Exposure of human immune cells to asbestos causes a reduction in antitumor immunity. The present study aimed to investigate the recovery of reduced antitumor immunity by several ingredients taken as supplements or foods, including trehalose (Treh) and glycosylated hesperidin (gHesp). Peripheral blood CD4+ cells were stimulated with IL2, antiCD3 and antiCD28 antibodies for 3 days, followed by further stimulation with IL2 for 7 days. Subsequently, cells were stimulated with IL2 for an additional 28 days. During the 28 days, cells were cultured in the absence or presence of 50 µg/ml chrysotile asbestos fibers. In addition, cells were treated with 10 mM Treh or 10 µM gHesp. Following culture for 28 days, reverse transcriptionquantitative PCR was performed to assess the expression levels of transcription factors, cytokines and specific genes, including matrix metalloproteinase7 (MMP7), nicotinamide nucleotide transhydrogenase (NNT) and CXC motif chemokine receptor 3, in unstimulated cells (fresh) and cells stimulated with PMA and ionomycin (stimuli). The results demonstrated that compared with the control group, chrysotileexposure induced alterations in MMP7, NNT and IL17A expression levels were not observed in the 'Treh' and 'gHesp' groups in stimulated cells. The results suggested that Treh and gHesp may reverse asbestos exposureinduced reduced antitumor immunity in T helper cells. However, further investigation is required to confirm the efficacy of future trials involving the use of these compounds with highrisk human populations exposed to asbestos, such as workers involved in asbestoshandling activities.
Asunto(s)
Amianto/efectos adversos , Linfocitos T CD4-Positivos/inmunología , Suplementos Dietéticos , Hesperidina/farmacología , Mesotelioma Maligno/inmunología , Trehalosa/farmacología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Células Cultivadas , Humanos , Interferón gamma/inmunología , Interleucina-17/inmunología , Masculino , Mesotelioma Maligno/inducido químicamente , Mesotelioma Maligno/prevención & control , Persona de Mediana Edad , Receptores CXCR3/inmunologíaRESUMEN
The effects of asbestos on immunocompetent cells have been investigated. In particular, attention was paid to regulatory T cell function, which was observed using the HTLV-1 immortalized human polyclonal T cell line MT-2. Exposure to asbestos (approximately more than 25 µg/mL for 1-3 day) induced apoptosis, and we observed an increase in regulatory T cell function and acceleration of the cell cycle with continuous exposure to low concentrations of asbestos (5-10 µg/mL for more than eight months). Furthermore, cDNA microarray analysis in this study revealed that expression of matrix metalloproteinase-7 (MMP-7) was markedly higher in exposed sublines compared to original MT-2 cells. It was determined that MMP-7 had no effect on Treg function, as determined by examination of sublines and by addition of recombinant MMP-7 and neutralizing antibodies or inhibitors of MMP-7. However, when examining melting of the extracellular matrix (an MMP-7-mediated event) or the extent to which the MT-2 parent strain or long-term exposed subline cells pass through a fibronectin-coated filter, more filter passes were observed for the subline. These results suggest that the effect of asbestos fibers on Treg cells results in excessive migration of the tumor microenvironment through hypersecretion of MMP-7 together with an increase in suppressive function and enhancement of cell cycle progression. Therefore, one possible way to prevent the development of asbestos-induced cancer is to reduce the function (including MMP-7 production) or amount of Treg cells by physiologically active substances or food ingredients. Alternatively, it may be possible to invoke immune checkpoint treatments when carcinogenesis occurs.
Asunto(s)
Amianto/toxicidad , Carcinógenos/toxicidad , Movimiento Celular/efectos de los fármacos , Metaloproteinasa 7 de la Matriz/biosíntesis , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/metabolismo , Línea Celular Transformada , Movimiento Celular/fisiología , HumanosRESUMEN
Asbestos exposure causes malignant tumors such as lung cancer and malignant mesothelioma. The effects of asbestos fibers on immunocompetent cells, however, have not been well studied. Asbestos physically comprises a fibrous substance, which differs from silica particles which are a particulate substance, although chemically it is a mineral silicate. Since silicosis patients previously exposed to silica particles often suffer from lung and autoimmune diseases, it is clear that silica exposure impairs immune tolerance. Similarly, asbestos may alter the immune system in asbestos-exposed individuals. Given that malignant tumors can result following exposure to asbestos, the attenuation of anti-tumor immunity in cases of asbestos exposure is an important area of investigation. We observed the effect of asbestos fibers on T lymphocytes, such as CD8+ cytotoxic T lymphocytes (CTLs), CD4+ helper T (Th), and regulatory T (Treg) cells, and showed that anti-tumor immunity was attenuated, as demonstrated in a system that stimulates fresh cells isolated from peripheral blood in vitro and a system that is continuously exposed to a cell line. In this manuscript, we introduce the experiments and results of studies on CTLs, as well as Th and Treg cells, and discuss how future changes in immunocompetent cells induced by asbestos fibers can be clinically linked.