• Molecular & Cellular Toxicology
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• v.1 no.2
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• pp.73-77
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• 2005

Nickel is the one of potent environmental, the occupational pollutants and the classified human carcinogens. It is a serious hazard to human health, when the metal exposure. To prevent human diseases from the heavy metals, it is seemingly important that understanding of how nickel exerts their toxicity and carcinogenic effect at a molecular and a genomic level. The process of nickel absorption has been demonstrated as phagocytosis, iron channel and diffusion. Uptaked nickel has been suggested to induce carcinogenesis via two pathways, a direct DNA damaging pathway and an indirect DNA damaging pathway. The former was originated from the ability of metal to generate Reactive Oxygen Species (ROS) and the reactive intermediates to interact with DNA directly. Ni-generated ROS or Nickel itself, interacts with DNAs and histones to cause DNA damage and chromosomal abnormality. The latter was originated from an indirect DNA damage via inhibition of DNA repair, or condensation and methylation of DNA. Cells have ability to protect from the genotoxic stresses by changing gene expression. Microarray analysis of the cells treated with nickel or nickel compounds, show the specific altered gene expression profile. For example, HIF-I (Hypoxia-Inducible Factor I) and p53 were well known as transcription factors, which are upregulated in response to stress and activated by both soluble and insoluble nickel compounds. The induction of these important transcription factors exert potent selective pressure and leading to cell transformation. Genes of metallothionein and family of heat shock proteins which have been known to play role in protection and damage control, were also induced by nickel treatment. These gene expressions may give us a clue to understand of the carcinogenesis mechanism of nickel. Further discussions on molecular and genomic, are need in order to understand the specific mechanism of nickel toxicity and carcinogenicity.

• Molecules and Cells
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• v.38 no.7
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• pp.657-662
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• 2015

Rapid and efficient engulfment of apoptotic cells is an essential property of phagocytes for removal of the large number of apoptotic cells generated in multicellular organisms. To achieve this, phagocytes need to be able to continuously uptake apoptotic cells. It was recently reported that uncoupling protein 2 (Ucp2) promotes engulfment of apoptotic cells by increasing the phagocytic capacity, thereby allowing cells to continuously ingest apoptotic cells. However, the functions of Ucp2, beyond its possible role in dissipating the mitochondrial membrane potential, that contribute to elevation of the phagocytic capacity have not been determined. Here, we report that the anion transfer or nucleotide binding activity of Ucp2, as well as its dissipation of the mitochondrial membrane potential, is necessary for Ucp2-mediated engulfment of apoptotic cells. To study these properties, we generated Ucp2 mutations that affected three different functions of Ucp2, namely, dissipation of the mitochondrial membrane potential, transfer of anions, and binding of purine nucleotides. Mutations of Ucp2 that affected the proton leak did not enhance the engulfment of apoptotic cells. Although anion transfer and nucleotide binding mutations did not affect the mitochondrial membrane potential, they exerted a dominant-negative effect on Ucp2-mediated engulfment. Furthermore, none of our Ucp2 mutations increased the phagocytic capacity. We conclude that dissipation of the proton gradient by Ucp2 is not the only determinant of the phagocytic capacity and that anion transfer or nucleotide binding by Ucp2 is also essential for Ucp2-mediated engulfment of apoptotic cells.

• Applied Microscopy
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• v.35 no.4
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• pp.84-90
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• 2005

Neutrophils that influx into the alveolar spaces from circulatory bloods play a important role in pathogenesis of acute lung injury. During the acute inflammatory phase, in order to investigate the acceleration of macrophage phagocytosis to the neutrophils is able to reduce the neutrophil-derived acute lung injury, endotoxemia was induced by insufflation of lipopolysaccharide intratracheally and organic germanium was injected intraperitoneally after endotoxin treatment. At 5 h after endotoxin treatment, lung weight and BAL protein concentration are significantly increased (p<0.001) compared to sham, and that was remarkedly decreased (p<0.001, p<0.01) by injection of germanium. In addition germanium treatment resulted to decreased the number of alveolar PMNs and to increase the percentage of engulfed neutrophils by alveolar macrophages. These observations indicate that organic germanium may have a role of reduction to neutrophil-derived acute lung injury in endotoxemia.

• The Journal of the Korean Society for Microbiology
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• v.35 no.1
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• pp.87-95
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• 2000

Staphylococcus aureus infections are often life-threatening. Relatively little is known about the host response to these infections, in particular, the implication of apoptosis induced by this microorganism. In this study, we have shown that S. aureus was cytotoxic to J774A.1 cell, a murine macrophage cell line. The cell death mediated by S. aureus occurred through apoptosis, as shown by increase in the proportion of fragmented host cell DNA. Although phagocytosis and NO production had important role in the induction of apoptosis, the contact between bacteria and host cells was not essential for this pathway. A certain bacterial product could also induce typical caspase-dependent apoptosis of J774A.1 cell. It is expected that new interpretation may be possible to host-parasite relationship based on these results.

• Journal of fish pathology
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• v.15 no.2
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• pp.65-75
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• 2002

This study was performed to know the effects of stress induced by the daily fluctuation of water temperture from 18$^{\circ}C$ to 25$^{\circ}C$ up and down for 30 days on the defence mechanism of olive flounder. Puralichthys olivaceus. To make clear the temperature stress on the defense mechanism of the tested fish. several factors of immune response such as counting of leucocyte appearance in peripheral blood, phagocytic activity in whole blood cells, nitroblue tetrazolium(NBT) reduction, chemiluminescence(CL) response, and lysozyme activity were investigated at 28 days after giving the change of water temperature. The fish was controlled under the none feeding condition during experimental period. Mortality of the tested fish was rapidly increased up to 22% within the first one week of the experimental period without any additional stress factors. The number of neutrophil of peripheral blood in the tested group was significantly higher than the control group at the 2nd week. but the number of lymphocyte was significantly lower than the control group at the 1st and 3rd day of the experimental period. respectively. In the NBT reduction test, the activity of macrophage in the control group fish was the highest on the 7th day while that in the tested group was on the 3rd day. Also. the phagocytosis of tested group against formalin killed cells was retarded compared with the control. CL response of the tested group was significantly lower from 2nd to 5lh day of the experimental period than the control. 'The lysozyme activity of tested group was remained higher during the experimental period than the control. Even though the tested fish showed different results in some non-specific factors of immune respceses between tested and control group fish, olive flounder seems highly adaptable in repealed water temperature change in condition after one week under the given temperature fluctuation range.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.9 no.1
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• pp.65-73
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• 2003

The researches for tumor and the developments for new anti-tumor medicine are being continuously developed in the oriental as well as the west. The principles therapy of anti-tumor activity was based on knowledge of the method of support the healthy energy and strengthen the body resistance, promote blood circulation to remove blood stasis, clear away heat and toxic materials, dissipate phlegm and disperse the accumulation of evils. But the major clinical features of tumor was to be considered in developing a treatment plan include (1) distinguish between clinical and pathologic staging - acute and chronic, (2) classification of pathologic pattern, and (3) distinction of body situation : for examples asthenia - sthenia etc. It was most important to distinguish between supporting the healthy and eliminating the evil factors and to treat differently at the root and the branch cause of a neoplasm. In clinical study and experimental study, the effects of oriental medicine could be summarized as three that were decreasing toxicity of chemo-therapy, directly suppressing and killing cancerous cell and increasing chemo-effect through preventing metastasis. Improving organic immunity with oriental medicine could be summarized as five that were promoting phagocytosis of macrophage, inducing interferon, promoting formation of immnoglobulin, increasing number of T-cell and promoting transformation of lymphocyte. It is suggested that effective use of immune activating herbs inhibited metastasis and decreased recurrence and then we were able to expect increasing survival rate and improving clinical symptoms and quality of life(QOL) of tumor patients.

• IMMUNE NETWORK
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• v.7 no.2
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• pp.57-65
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• 2007

Background: Cordyceps militaris have been reported to modify the immune and inflammatory responses both in vivo and in vitro. Macrophages play important roles in the innate immunity through the phagocytosis of antigens. This study examined the effects of Cordyceps militaris on the activation of murine macrophage RAW 264.7 cells and primary macrophages. Methods: The components contained in culture broth of Cordyceps militaris were purified by propyl alcohol extraction and HP 20 column chromatography to CMDB, CMDBW, CMDB5P, and CMDB25P. The amounts of nitric oxide (NO) were determined by using ELISA, Griess reagent respectively. The amounts of some cytokines were determined by using ELISA, western blot, and RT-PCR The expression levels of cell surface molecules (ICAM-1, B7-1 and B7-2) were measured by flow cytometric analysis. Results: All the components of Cordyceps militaris produced significant amounts of NO. In particular, CMDB produced much more NO in RAW 264.7 cells and primary macrophages than other fractions of Cordyceps militaris. CMDB increased significantly the production of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$, and IL-6 dose-dependently in RAW 264.7 cells. Examination of the gene expression level also showed that the enhanced production of cytokines was correlated with the up-regulation of i-NOS expression, cycloxygenase (COX)-2 expression, IL-1${\beta}$ and IL-6 expression, and TNF-${\alpha}$ expression on the expression of mRNAs by semi-quantitative RT-PCR Western blot analysis also confirmed that CMDB enhances the expression level of these cytokines. Conclusion: These results show that CMDB stimulates the production of NO and pro-inflammatory cytokines and can also up-regulate the gene expression levels in macrophages.

• IMMUNE NETWORK
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• v.8 no.3
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• pp.67-74
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• 2008

Background: The effects of the dietary administration of two heat-inactivated whole bacteria from the Vibrionaceae family, singly or combined, on innate immune response of the rainbow trout were studied. The two bacteria (Pdp11 and 51M6), which were obtained from the skin of rainbow trout, showed in vitro characteristics that suggested they could be considered as potential fish probiotics. Methods: The fish were fed four different diets: control (non-supplemented), or diets supplemented with heat-inactivated bacteria at $10^8$ cfu/g Pdp11, $10^8$ cfu/g 51M6 or with $0.5{\times}10^8$ cfu/g Pdp11 plus $0.5{\times}10^8$ cfu/g 51M6 for 4 weeks. Six fish were sampled at weeks 1, 2, 3 and 4, and then the main humoral (natural haemolytic complement activity and serum peroxidase content) and cellular innate immune responses (leucocyte peroxidase content, phagocytosis, respiratory burst and cytotoxicity) were evaluated. Results: The serum peroxidase content and the natural haemolytic complement activity increased with time, reaching the highest values in the third and fourth weeks of feeding, respectively. The phagocytic ability of specimens fed the mixture of the two inactivated bacteria was significantly higher than in the controls after 2 and 3 weeks of treatment. The same activity increased significantly in rainbow trout fed the Pdp11 diet for 2 weeks or the 51M6 diet for 3 weeks. Respiratory burst activity was unaffected by all the experimental diets at all times assayed. Cytotoxic activity had significantly increased after 3 weeks in fish fed the 51M6 diet. Conclusion: Our results demonstrated the usefulness of incorporating inactivated probiotic bacteria into fish diets.

• Parasites, Hosts and Diseases
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• v.52 no.4
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• pp.355-365
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• 2014

The enteric protozoan parasite Entamoeba histolytica is the causative agent of human amebiasis. During infection, adherence of E. histolytica through Gal/GalNAc lectin on the surface of the amoeba can induce caspase-3-dependent or -independent host cell death. Phosphorylinositol 3-kinase (PI3K) and protein kinase C (PKC) in E. histolytica play an important function in the adhesion, killing, or phagocytosis of target cells. In this study, we examined the role of amoebic PI3K and PKC in amoeba-induced apoptotic cell death in Jurkat T cells. When Jurkat T cells were incubated with E. histolytica trophozoites, phosphatidylserine (PS) externalization and DNA fragmentation in Jurkat cells were markedly increased compared to those of cells incubated with medium alone. However, when amoebae were pretreated with a PI3K inhibitor, wortmannin before being incubated with E. histolytica, E. histolytica-induced PS externalization and DNA fragmentation in Jurkat cells were significantly reduced compared to results for amoebae pretreated with DMSO. In addition, pretreatment of amoebae with a PKC inhibitor, staurosporine strongly inhibited Jurkat T cell death. However, E. histolytica-induced cleavage of caspase-3, -6, and -7 were not inhibited by pretreatment of amoebae with wortmannin or staurosporin. In addition, we found that amoebic PI3K and PKC have an important role on amoeba adhesion to host compartment. These results suggest that amebic PI3K and PKC activation may play an important role in caspase-independent cell death in Entamoeba-induced apoptosis.

• Parasites, Hosts and Diseases
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• v.46 no.4
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• pp.217-221
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• 2008

Free-living Naegleria fowleri leads to a fatal infection known as primary amebic meningoencephalitis in humans. Previously, the target cell death could be induced by phagocytic activity of N. fowleri as a contact-dependent mechanism. However, in this study we investigated the target cell death under a non-contact system using a tissue-culture insert. The human microglial cells, U87MG cells, co-cultured with N. fowleri trophozoites for 30 min in a non-contact system showed morphological changes such as the cell membrane destruction and a reduction in the number. By fluorescence-activated cell sorter (FACS) analysis, U87MG cells co-cultured with N. fowleri trophozoites in a non-contact system showed a significant increase of apoptotic cells (16%) in comparison with that of the control or N. fowleri lysate. When U87MG cells were co-cultured with N. fowleri trophozoites in a non-contact system for 30 min, 2 hr, and 4 hr, the cytotoxicity of amebae against target cells was 40.5, 44.2, and 45.6%, respectively. By contrast, the cytotoxicity of non-pathogenic N. gruberi trophozoites was 10.2, 12.4, and 13.2%, respectively. These results suggest that the molecules released from N. fowleri in a contact-independent manner as well as phagocytosis in a contact-dependent manner may induce the host cell death.