ABSTRACT
Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is easily introduced to humans via consumption of grilled or smoked meat. BaP causes harmful oxidative effects on cell development, growth and survival through an increase in membrane lipid peroxidation, oxidative DNA damage and mutagenesis. Therefore, the present study was conducted to evaluate the synergistic effects of BaP on oxidative stress in hepatic tumors. In this study, we established a hepatic tumor model by injecting rat hepatoma N1-S1 cells into healthy rats. Changes in the abundance of heat shock proteins (HSPs), antioxidant enzymes and pro-inflammatory cytokines were then investigated by western blot analysis. In addition, we examined changes in oxidative stress levels. Injection of N1-S1 cells or concomitant injection of BaP and N1-S1 cells resulted in the formation of hepatic tumors at the injection site. Evaluation of rat plasma reveals that hepatic tumors induced by BaP and N1-S1 cells expresses higher levels of Hsp27, superoxide dismutase (SOD), and tumor necrosis factor-alpha (TNF-alpha) when compared to those induced by N1-S1 cells only. The collective results of this study suggest that BaP exerts synergistic effects on the expression of HSP, cytokines and antioxidant enzymes in hepatic tumors induced by rat hepatoma N1-S1 cells.
Subject(s)
Animals , Humans , Male , Rats , Antioxidants/metabolism , Benzo(a)pyrene/pharmacology , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor/drug effects , Cytokines/metabolism , Heat-Shock Proteins/metabolism , Liver Neoplasms/enzymology , Neoplasms, Experimental/metabolism , Oxidative Stress/drug effects , Rats, Sprague-DawleyABSTRACT
Xenotransplantation, the transplantation of cells, tissues or organs between individuals of different species, would resolve the current shortage of organs, but rejection remains the major hurdle to successful xenotransplantation. In the present study, we analyzed mixed lymphocyte reactions (MLRs) and used 51Cr release assays in order to identify the proliferation and expansion of mouse CD8+ cytotoxic T lymphocyte cells against PK15, PK15/pIL-18 or PK15/mIL-18 cells. In addition, we identified T cell populations in mouse splenocytes and lymph node cells using two-color flow cytometry. It was found that the CD8+T cells of xenograft recipients proliferated extensively and that the survival rates of populations of PK15/mIL-18 or PK15/pIL-18 cells were higher than untransfected controls. Moreover, CD3+T cells were increased in mice injected with PK15 cells or PK15/pIL-18 cells but PK15/pIL-18 cell numbers were lower in lymph nodes than untransfected controls. CD8+T cells numbers were reduced in the lymph nodes of PK15/pIL-18 injected mice. These results suggest that porcine IL-18 regulates anti-pig cellular rejection in C57BL/6 mice.
Subject(s)
Mice , Female , Animals , Transplantation, Heterologous , Transplantation , Transgenes/immunology , Transfection , Tissue Distribution , T-Lymphocytes/metabolism , Swine , RNA, Messenger/metabolism , Phenotype , Mice, Inbred C57BL , Lymphocyte Culture Test, Mixed , Lymphocyte Activation , Kidney/cytology , Interleukin-18/genetics , Immunosuppression Therapy/methods , Graft Rejection/immunology , Genetic Vectors/chemical synthesis , Epithelial Cells/drug effects , Cytokines/metabolism , Cells, CulturedABSTRACT
In the early host defense system, effector function of natural killer (NK) cells results in natural killing against target cells such as microbe-infected, malignant, and certain allogenic cells without prior stimulation. NK cell cytotoxicity is selectively regulated by homeostatic prevalence between a repertoire of both activating and inhibitory receptors, and the discrimination of untransformed cells is achieved by recognition of major histocompatibility complex (MHC) class I alleles through inhibitory signals. Although it is well known that the bipotential T/NK progenitors are derived from the common precusor, functional mechanisms in terms of the development of NK cells remain to be further investigated. NK cells are mainly involved in innate immunity, but recent studies have been reported that they also play a critical role in adaptive immune responses through interaction with dendritic cells (DC). This interaction will provide effector functions and development of NK cells, and elucidation of its precise mechanism may lead to therapeutic strategies for effective treatment of several immune diseases.
Subject(s)
Adaptive Immunity , Alleles , Dendritic Cells , Discrimination, Psychological , Homicide , Immune System Diseases , Immunity, Innate , Killer Cells, Natural , Major Histocompatibility Complex , PrevalenceABSTRACT
BACKGROUND: Bone marrow stromal cells (BMSCs) express many cell surface molecules, which regulate the proliferation and differentiation of immune cells within the bone marrow. METHODS: To identify cell surface molecules, which can regulate cell proliferation through cell interaction, monoclonal antibodies (MoAbs) against BMSCs were produced. Among them, 1H8 MoAb, which recognized distinctly an 80 kDa protein, abolished myeloma cell proliferation that was induced by co-culturing with BMSCs. RESULTS: IL-6 gene expression was increased when myeloma or stromal cells were treated with 1H8 MoAb. In addition, the expression of IL-6 receptor and CD40 was up-regulated by 1H8 treatment, suggesting that the molecule recognized by 1H8 MoAb is involved in cell proliferation by modulating the expression of cell growth-related genes. Myeloma cells contain high levels of reactive oxygen species (ROS), which are related to gene expression and tumorigenesis. Treatment with 1H8 decreased the intracellular ROS level and increased PAG antioxidant gene concomitantly. Finally, 1H8 induced the tyrosine phosphorylation of several proteins in U266. CONCLUSION: Taken together, 1H8 MoAb recognized the cell surface molecule and triggered the intracellular signals, which led to modulate gene expression and cell proliferation.
Subject(s)
Humans , Antibodies, Monoclonal , Bone Marrow , Carcinogenesis , Cell Communication , Cell Proliferation , Gene Expression , Interleukin-6 , Mesenchymal Stem Cells , Phosphorylation , Reactive Oxygen Species , Receptors, Interleukin-6 , Stromal Cells , TyrosineABSTRACT
No abstract available.
Subject(s)
Cell Line , Cell Proliferation , Cytokines , Leukemia, Erythroblastic, AcuteABSTRACT
No abstract available.