These findings indicate that asbestos exposure has the potential to influence immune responses, which may be associated with the pathogenesis of MM following exposure to asbestos. Consideration of the relationship between alteration of immune responses and pathogenesis of mesothelioma may indicate that asbestos exposure has the potential to cause impairment of tumor immunity; transformed cells may be able to escape tumor immunity and develop MM (5,9C11). of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1, IL-1, IL-3, IL-5, IL-13 and IL-17A in supernatants. Individual administration of these cytokines, excluding G-CSF and GM-CSF, led to an increase in cell growth of MeT-5A, whereas this effect was not observed following the combined administration of these cytokines. The results indicate that cytokines secreted by immune cells upon exposure to asbestos cause an increase in the growth activity of mesothelial cells, suggesting that alterations in the production of cytokines by immune cells may contribute to tumorigenesis in individuals exposed to asbestos. (6). Most recently, we reported that asbestos exposure suppressed the induction of cytotoxic T lymphocytes during a mixed lymphocyte reaction (8). These findings indicate that asbestos exposure has the potential to influence immune responses, which may be associated with the pathogenesis of MM following exposure to asbestos. Consideration of the relationship between alteration of immune responses and pathogenesis of mesothelioma may indicate that asbestos exposure has the potential to cause impairment of tumor immunity; transformed cells may be able to escape tumor immunity and develop MM (5,9C11). Alternatively, altered production of cytokines by immune cells Punicalagin upon exposure to asbestos is usually another potential mechanism that may contribute to the pathogenesis of mesothelioma. It is possible that cytokines produced by immune cells existing in or migrating into the pleural cavity, or cytokines transported through the blood stream following their production in lymphoid organs, may affect the function of pleural cells (11C15). Previous studies have reported high serum levels of granulocyte colony-stimulating factor (G-CSF), transforming growth factor , Rabbit polyclonal to EIF4E interleukin (IL)-6 and IL-10 in patients with mesothelioma (16C18). However, it is still unknown whether cytokines derived from immunocompetent cells exposed to asbestos influence normal mesothelial cells. Therefore, in the current study, peripheral blood mononuclear cells (PBMCs) from healthy donors were directly exposed to asbestos under stimulation with antibodies against CD3 and CD28, and the effects of the resulting culture supernatants around the cell growth of mesothelial cells were examined (19). The results exhibited that supernatants from PBMC cultures upon exposure to 20 g/ml of asbestos for 7 days significantly enhanced the cell growth of MeT-5A, and exhibited markedly higher levels of IL-1, IL-1, IL-3, IL-5, IL-13 and IL-17A. These cytokines are often reported as pro-inflammatory cytokines (22). In addition, these cytokines were confirmed to be able to enhance the proliferation of MeT-5A cells. Collectively, these results indicate that cytokines secreted by immune cells upon exposure to asbestos cause an increase in the growth activity of mesothelial cells, suggesting the possibility that pleural cells may be influenced by these cytokines in individuals exposed to asbestos. It is often reported that chronic inflammation has the potential to contribute to carcinogenesis; however, this mechanism is usually complex (23,24). Inhalation of asbestos also causes inflammatory responses that include production of free radicals and cytokines, as well as induction of cell death, which is usually thought to be important carcinogenesis resulting from asbestos exposure (25). One notable finding from the present study is the relationship between immune cells and mesothelial cells as mediated by IL-1 and IL-1, which are representative types of inflammatory cytokines. IL-1 and IL-1 have a biologically Punicalagin comparable function and promote tumor angiogenesis, invasion and metastasis through activating nuclear factor-B (26). Alveolar macrophages collected from asbestosis patients exhibit increased levels of IL-1 (27). It is well known that asbestos can induce activation of Punicalagin caspase-1 mediated by the NLRP3 inflammasome; IL-1 is usually produced by cleavage of the inactive pro-IL-1 precursor by caspase-1 (28,29). Punicalagin IL-5 was originally identified as a B-cell growth factor in mice. IL-5 stimulates B-cell proliferation and activation, and regulates eosinophil differentiation through Ras-mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase and Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathways (30). IL-5 is Punicalagin critical in allergic diseases, such as asthma and rhinitis; however, little is known with regard to the effects of IL-5 on mesothelial cells. Several studies have reported that IL-5 is one of the cytokines that exhibits increased levels in asbestos-exposed murine bronchoalveolar lavage (BAL) fluid (31,32). IL-5 is usually upregulated in invasive bladder cancer and stimulates the invasion of bladder cancer cell lines through the Ras-MAPK and JAK-STAT pathways, which are also important in MM.