• 대한의생명과학회지
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• 제20권4호
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• pp.194-200
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• 2014

Ginsan, polysaccharide isolated from the root of Panax ginseng C.A. Meyer, has been shown to be a potent immunomodulator, producing several cytokines and stimulating lymphoid cells to proliferate. In this study, ginsan was orally inoculated into BALB/c mice up to 39 days and the activity of immune cells containing macrophages and T cells was analyzed. Moreover, the production of cytokines, e.g., tumor necrotic factor-${\alpha}$ (TNF-${\alpha}$), interferon-${\gamma}$ (IFN-${\gamma}$), GM-CSF and IL-12 was also analyzed. In results, the phagocytosis of macrophages was increased. About 13% cytotoxicity of NK cells was observed in 22 days and 29 days of administration. But, oral administration did not highly affect the proliferation of T cells. In cytokine analysis, 150 mg/kg and 300 mg/kg at 22 days and 29 days showed three times more increase in TNF-${\alpha}$ than the controls. IFN-${\gamma}$ showed 1.07 and 1.16 times more increase at 150 mg/kg and 300 mg/kg over 22 days, respectively more than the controls. 32 days of 150 mg/kg and 300 mg/kg induced GM-CSF of about 1.3 times more than the controls. IL-12 was not induced in samples more than the controls. Ginsan could be a potential immunostimulator. Therefore, our study suggests that it can be adapted as an immunostimulator that requires a relatively short oral administration.

• Molecular & Cellular Toxicology
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• 제1권2호
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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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• 제38권7호
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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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• 제35권4호
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• pp.84-90
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• 2005

호중구는 다양한 원인에 의해서 발생되는 급성 폐 손상의 발병기전에 중요한 역할을 담당한다. 폐 손상 시 순환계로부터 유입된 호중구들에 대한 폐포강 대식세포의 탐식작용이 증가될 경우 손상기전에 미치는 영향을 알아 보기 위해 내독소를 흰쥐의 기관지 내로 분무하고 유기게르마늄을 복강으로 투여하였다. 실험 결과 내독소 투여 5시간 후 체중당 폐 무게와 폐 세척액 내 단백질 함량은 유의하게 (p<0.001) 증가되었으나, 게르마늄 병행 투여로 폐 무게와 단백질 함량은 현저하게 (p<0.001, p<0.01) 감소되었다. 내독소 투여군은 폐 손상과 함께 폐포강 내 호중구는 유의하게 (p<0.05) 증가되었으나, 게르마늄의 투여로 감소되었고 폐포강 내 탐식된 호중구의 비율은 증가되었다. 이와 같은 결과들을 볼 때, 유기 게르마늄은 내독소증에 의한 급성 폐 손상에서 폐포강 대식세포들의 호중구 탐식작용을 증가시켜 폐 손상을 감소시킬 수 있는 것으로 나타났다.

• 대한미생물학회지
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• 제35권1호
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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.

• 한국어병학회지
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• 제15권2호
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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.

• 대한한방종양학회지
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• 제9권1호
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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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• 제7권2호
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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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• 제8권3호
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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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• 제52권4호
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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.