• 동의생리병리학회지
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• 제18권4호
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• pp.995-1000
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• 2004

This study was purposed to investigate the effect of Gamgung-tang(GGT) on immune responses induced by glucocorticoid in mice. GGT solution was treated by intraperitoneal injection for 7 days after glucocorticoid treatment(80㎎/㎏). And then B and T cell proliferation and cytolytic activity of natural killer(NK) cells were measured. There was 25% inhibition in B cell proliferation with treatment of glucocorticoid. However, B cell proliferation was not influenced by GGT treatment. T cell proliferation was also inhibited by 18.4% with treatment of glucocorticoid. On the other hand, T cell proliferation was increased dose-dependent manner in GGT treated group. Furthermore in purified T cell, the proliferation was furtherly increased than non-purified T cell. At concentration of 18㎎/mouse GGT, purified T cell proliferation was increase to above level of normal group. The cytotoxic activity of NK cell was decreased by 35.3% with treatment of glucocorticoid. In GGT treated group, the cytotoxic activity of NK cell was increased to the normal level. In purified NK cell, the cytolytic activity of NK cell was further increased than non-purifed NK cell. These results suggest that GGT may proliferate T cell that is suppressed by glucocorticoid, and activate NK cell activity.

• Journal of Acupuncture Research
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• 제32권1호
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• pp.79-88
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• 2015

Objectives : The purpose of this research was to investigate the cytotoxic effect of Natural Killer(NK)-92 cell and Snake Venom, and to elucidate its mechanism on human lung carcinoma cell A549. Methods : In order to figure out whether Snake Venom enhances the cytotoxic effect of NK-92 cell in A549 cell, Cell Viability Assay was conducted. Also, in order to observe the changes of Caspase-3 and Caspase-8, both of which are proteinases that advance apoptosis, and the changes of TNRF and DR3, which are Death Receptors of the extrinsic pathway of apoptosis, Western Blot Analysis was conducted. By conducting RT-PCR analysis, we have tried to confirm Perforin, Granzyme B, and GADPH, all of which are cytotoxic-related proteins. Lastly, in order to observe the effect of Snake Venom on NO formation within human lung carcinoma cells, NO determination was conducted. Results : 1. After conducting Cell Viability Assay, Snake Venom enhanced the cytotoxic effect of NK-92 cell and inhibited the growth of A549. 2. Western Blot Analysis caused proteinases Caspase-3 and Caspase-8, which advance apoptosis, to increase in the combined treatment group, but not in treatment groups that focused only on either Snake Venom or NK-92 cell in A549 lung carcinoma cells. 3. Western Blot Analysis caused an expression of TNFR2 and DR3, both of which are Death Receptors of the apoptosis extrinsic pathway, in the combined treatment group, but not intreatment groups that focused only on either Snake Venom or NK-92 cell in A549 human lung carcinoma cells. 4. After conducting NO determination, NO formation within A549 cell showed no significant changes in both treatment groups that focused NK-92 cell and combined treatment group. 5. After conducting RT-PCR, the expression of Granzyme B and Perforin, which are cytotoxic-related proteins within A549 human lung carcinoma cells, showed growth in the combined treatment group, but not the treatment group that focused only on NK-92 cell. Conclusion : It has been indicated that, when it comes to the A549 cell, Snake Venom enhances the increase of Death Receptor expression and continuous apoptosis reaction, leading to the enhancement of the cancer cell cytotoxic effect of the NK-92 cell. It is expected that Snake Venom can be used with the NK-92 cell for further lung cancer treatment.

• Journal of Acupuncture Research
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• 제19권6호
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• pp.111-124
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• 2002

A line of study reported that electroacupuncture(EA) modulate natural killer cell(NK Cell) activities. One report suggested that EA enhanced splenic interferon-gamma($IFN-{\gamma}$), interleukin-2(IL-2), and NK cell activity in Sprague-Dawley rats. Another study suggested that $IFN-{\gamma}$ mediates the up-regulation of NK cell activity, and endogenous ${\beta}$-endorphin secretion also play a role in the up-regulation of NK cell activity induced by EA stimulation. In order to better understand the molecular regulation underlying the activation of NK cell induced by EA, we have utilized cDNA microarray to elucidate how EA alters program of gene expression of spleen in rats. First, we divided three groups, group I was EA group treated with EA in restriction holder, group II was sham group with only holder stress, and last group III was control group with no treatment. We measured NK cell activity after EA stimulation three times for 2 days using $^{51}Cr$ release assay. Second, Biotin-labeled cDNA probes synthesized from EA group and sham group, were competitively hybridized to the microarray that contained variable genes. Such high-throughput screening has identified a number of EA-responsive gene candidates. Of these, we found that EA induced a subset of genes of genes that functionally could modulatory effects on NK cell activity. Genes(vascular cell adhesion molecule-1, protein-tyrosine kinase, CD94 mRNA) related to boost NK cell activity, were increased by EA And, genes(protein-tyrosine-phospatase mRNA, protein-tyrosine phosphatase(SHP-1) mRNA) related to inhibit NK cell activity, were decreased by EA. These EA-responsive genes may provide key insights from which to understand mechanisms of activation of NK cell induced by EA.

• 혜화의학회지
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• 제21권1호
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• pp.87-96
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• 2012

Aim : Natural killer (NK) cells are cytotoxic lymphocytes that lyse certain tumor- and virus-infected cells without any prior stimulation or immunization. This article aims to review the significance of evaluating peripheral blood NK cells to predict anti-tumor immune function and prognosis in cancer patients. Methods : PubMed was used to create a database for this review. Search words of cancer, natural killer cell, prognosis were used to retrieve related articles. References of the collected articles were also reviewed. Results : Current evidence indicates that decreased or absent NK cell count or activity is mostly associated with the development or progression of cancer. In patients with various types of cancer, NK cell activity was mostly associated with the cancer prognosis and survival despite some conflicting results. Conclusion : The data shows the evaluation of anti-tumor immunity in cancer patients through natural killer cell measurement still remains a controversial matter. However, it is clear that the NK cell activity plays an important role in cancer and is associated with prevention of both early stage and metastatic cancer.

• Animal cells and systems
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• 제4권4호
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• pp.341-345
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• 2000

It has been very difficult to develop and evaluate efficient fish vaccines because fish immune cells have not been properly characterized. In this study, we investigated the cell-mediated immunological properties of B- and T-like cells in Nile tilapia (Oreochromis nilotica). Surface immunoglobulin negative ($slg^{-}$) cell population proliferated in response to mammalian T-cell mitogens PHA and Con A, while surface immunoglobulin positive ($slg^{+}$) cells responded to the B-cell mitogen LPS. The slg$^{[-10]}$ cells from hemocyanin (HC)-immunized Tilapia, compared to the non-immunized control, reacted more to PHA than to Con A. Unexpectedly, antigen (Ag)-specific response was observed in both $slg^{-}$ and $slg^{-}$cells. Regardless of HC immunization, whole leukocytes from 8 head kidney of fish showed natural killer (NK)cell activity. Especially, NK cell activity was much higher in slg$^{[-10]}$ cells than in slg$^{+}$cells, indicating the possibility that fish NK cells were not at least associated with slg$^{+}$ cell population and not activated by Ag. Further understanding of functional fish immune cells will help to evaluate and develop effective vaccines for fishes and to monitor the course of therapy In infected fishes.hes.

• Biomolecules & Therapeutics
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• 제22권2호
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• pp.106-113
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• 2014

In the present study, we investigated anti-cancer effect of snake venom activated NK cells (NK-92MI) in lung cancer cell lines. We used snake venom ($4{\mu}g/ml$) treated NK-92MI cells to co-culture with lung cancer cells. There was a further decrease in cancer cell growth up to 65% and 70% in A549 and NCI-H460 cell lines respectively, whereas 30-40% was decreased in cancer cell growth by snake venom or NK-92MI alone treatment. We further found that the expression of various apoptotic proteins such as that Bax, and cleaved caspase-3 as well as the expression of various death receptor proteins like DR3, DR4 and Fas was also further increased. Moreover, consistent with cancer cell growth inhibition, the DNA binding activity of NF-${\kappa}B$ was also further inhibited after treatment of snake venom activated NK-92MI cells. Thus, the present data showed that activated NK cells could further inhibit lung cancer cell growth.

• BMB Reports
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• 제52권12호
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• pp.718-727
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• 2019

Severe combined immunodeficiency (SCID) is a group of inherited disorders characterized by compromised T lymphocyte differentiation related to abnormal development of other lymphocytes [i.e., B and/or natural killer (NK) cells], leading to death early in life unless treated immediately with hematopoietic stem cell transplant. Functional NK cells may impact engraftment success of life-saving procedures such as bone marrow transplantation in human SCID patients. Therefore, in animal models, a T cell-/B cell-/NK cell+ environment provides a valuable tool for understanding the function of the innate immune system and for developing targeted NK therapies against human immune diseases. In this review, we focus on underlying mechanisms of human SCID, recent progress in the development of SCID animal models, and utilization of SCID pig model in biomedical sciences. Numerous physiologies in pig are comparable to those in human such as immune system, X-linked heritability, typical T-B+NK- cellular phenotype, and anatomy. Due to analogous features of pig to those of human, studies have found that immunodeficient pig is the most appropriate model for human SCID.

• BMB Reports
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• 제52권11호
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• pp.625-634
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• 2019

Severe combined immunodeficiency (SCID) is a group of inherited disorders characterized by compromised T lymphocyte differentiation related to abnormal development of other lymphocytes [i.e., B and/or natural killer (NK) cells], leading to death early in life unless treated immediately with hematopoietic stem cell transplant. Functional NK cells may impact engraftment success of life-saving procedures such as bone marrow transplantation in human SCID patients. Therefore, in animal models, a T cell-/B cell-/NK cell＋ environment provides a valuable tool for understanding the function of the innate immune system and for developing targeted NK therapies against human immune diseases. In this review, we focus on underlying mechanisms of human SCID, recent progress in the development of SCID animal models, and utilization of SCID pig model in biomedical sciences. Numerous physiologies in pig are comparable to those in human such as immune system, X-linked heritability, typical T-B＋NK- cellular phenotype, and anatomy. Due to analogous features of pig to those of human, studies have found that immunodeficient pig is the most appropriate model for human SCID.

• Molecular Medicine Reports
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• 제20권4호
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• pp.3301-3307
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• 2019

c-Myc is a characteristic oncogene with dual functions in cell proliferation and apoptosis. Since the overexpression of the c-Myc proto-oncogene is a common event in the development and growth of various human types of cancer, the present study investigated whether oncogenic c-Myc can alter natural killer (NK) cell-mediated immunity through the expression of associated genes, using PCR, western blotting and flow cytometry assays. Furthermore, whether c-Myc could influence the expression levels of natural killer group 2 member D (NKG2D) ligands, which are well known NK activation molecules, as well as NK cell-mediated immunity, was investigated. c-Myc was inhibited by 10058-F4 treatment and small interfering RNA transfection. Upregulation of c-Myc was achieved by transfection with a pCMV6-myc vector. The inhibition of c-Myc increased MHC class I polyeptide-related sequence B and UL16 binding protein 1 expressions among NKG2D ligands, and the overexpression of c-Myc suppressed the expression of all NKG2D ligands, except MHC class I polyeptide-related sequence A. Furthermore, the alteration of c-Myc activity altered the susceptibility of K562 cells to NK cells. These results suggested that the overexpression of c-Myc may contribute to the immune escape of cancer cells and cell proliferation. Combined treatment with NK-based cancer immunotherapy and inhibition of c-Myc may achieve improved therapeutic results.

• Journal of Acupuncture Research
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• 제31권1호
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• pp.111-119
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• 2014

Objectives : I investigated whether Bee Venom can synergistically strengthen the cytotoxic effects of NK-92 cells, enhancing the inhibition of the growth of Lung Cancer Cells including A549 and NCI-H460 through induction of death receptor dependent extrinsic apoptosis and NO generation in the Nitro-oxide pathway. Methods : Bee Venom inhibited cell proliferation of A549 or NCI-H460 Human Lung Cancer Cells as well as NK-92 Cells. Moreover, when they were co-punctured with NK cells and concomitantly treated by 3 ${\mu}g/ml$ of Bee Venom, more influence was exerted on inhibition of proliferation of A549 or NCI-H460 Human Lung Cancer Cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2, DR3, DR6 in A549 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells and treatment of 3 ${\mu}g/ml$ of Bee Venom, compared to co-culture of NK-92 cells alone, whereas the expression of Fas, TNFR2, DR6 in NCI-H460 Lung Cancer Cells was significantly increased by co-culture of NK-92 cells, representing no synergistic effects in the co-culture of NK-92 cell and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom. Coincidently, caspase-8, a expression of pro-apoptotic proteins in the extrinsic apoptosis pathway demonstrated same results as the above. Meanwhile, In NO generation, there is little change of NO generation in co-culture of NK-92 cells with A549 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, whereas increase of NO generation was shown in co-culture of NK-92 cells with NCI-H460 cells as well as the co-culture of NK-92 cell with them and concomitant treatment of 3 ${\mu}g/ml$ of Bee Venom, although synergistic effects by Bee Venom was not found. Conclusions : These present data provide that Bee Venom could be useful candidate compounds to enhance lung cancer growth inhibiting ability of NK-92 cells through DR expression and the related apoptosis.