• The Journal of Internal Korean Medicine
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• v.19 no.2
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• pp.208-218
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• 1998

To clarify the activating effects of Buthus martensi Karsch on immunological function, its effect on primary and secondary antibodies production in mice of various ages was investigated. Buthus martensi Karsch increased the number of both antibody producing cells(anti-IgM and anti-IgG producing plaque forming cells, PFC) and phagocytic activity of peritoneal macrophage. Futhermore, these phenomena were significantly increased with aging in mice. Buthus martensi Karsch also increased natural killer cell activity concerning to cancer immunology. These results suggest that Buthus martensi Karsch markedly increases the reduced activity in the elderly and activates the immune response in senescence mice.

• Archives of Pharmacal Research
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• v.22 no.3
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• pp.255-261
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• 1999

The effect of biphenyl dimethyl dicarboxylate (PMC) on the cellular and nonspecific immunosuppressions by ketoconazole (KCZ) was investigated in ICR mice. PMC at a dose of 6 mg/kg was administered orally to mice daily for 14 consecutive days. KCZ was suspended in RPMI 1640 medium and orally administered at 160 mg/kg/day 2 hrs after the administration of PMC. Immune responses of the delayed-type hypersensitively (DTH) reaction to sheep red blood cells (SRBC), phagocytic activity and natural killer (NK) cell activity were evaluated. DTH reaction to SRBC was enhanced to normal level by the combination of PMC and KCZ, as compared with treatment of KCZ alone. In the combination of PMC and KCZ, as compared with treatment of KCZ alone, there were also significant increases in activities of natural killer (NK) cells and phagocytes along with circulating leukocytes. These findings indicate that PMC shows a significant restoration from the immunotoixc status induced by KCZ.

• Natural Product Sciences
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• v.2 no.1
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• pp.29-36
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• 1996

This study was to evaluate the antitumor and immunopotentiation effects of Manda Enzyme (ME). Oral administration of ME (0.2ml/mouse) to tumor bearing mice significantly prolonged survival rate compared to the control group with the prolongation ratio of 40%. The inhibition ratios for the first and the second experiments were 51.8% and 26.4%, respectively. Only the spleen index was significantly increased in the MEF-treated group, but not in the control group. Gamma globulin level of the MEF-treated group was elevated when mice were injected with sarcoma-180 cells on the left groin. Activities of natural killer (NK) and lymphokineactivated killer (LAK) cells were observed by $^{51}Cr-release$ method. Activities of NK cell against YAC-1 cells were significantly increased in the MEF treated group. And LAK cell activities against P815 cells were also significantly increased in the experimental group. These observations, therefore, suggest that ME may have an anticancer effect and immunopotentiating effect in vivo.

• Molecular Medicine Reports
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• v.20 no.4
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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.

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
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• 2001.10a
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• pp.6-9
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• 2001

• BMB Reports
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• v.50 no.5
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• pp.263-268
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• 2017

${\beta}$-Agarase cleaves the ${\beta}$-1,4 linkages of agar to produce neoagarooligosaccharides (NAO), which are associated with various physiological functions. However, the immunological functions of NAO are still unclear. In this study, we demonstrated that ${\beta}$-agarase DagA-produced neoagarohexaose (DP6), an NAO product, promoted the maturation of dendritic cells (DCs) by Toll-like receptor 4 (TLR4). DP6 directly and indirectly enhanced the activation of natural killer (NK) cells in a TLR4-dependent manner in vitro and in vivo. Finally, the antitumor activity of DP6 against B16F1 melanoma cells was inhibited in NK cell-depletion systems by using NK-cell depleting antibodies in vivo. Collectively, the results indicated that DP6 augments antitumor immunity against B16F1 melanoma cells via the activation of DC-mediated NK cells in a TLR4-dependent manner. Thus, DP6 is a potential candidate adjuvant that acts as an immune cell modulator for the treatment of melanoma.

• IMMUNE NETWORK
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• v.8 no.2
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• pp.53-58
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• 2008

Background: Molecular mechanisms of natural killer (NK) cell development from hematopoietic stem cells (HSCs) have not been clearly elucidated, although the roles of some genes in NK cell development have been reported previously. Thus, searching for molecules and genes related NK cell developmental stage is important to understand the molecular events of NK cell development. Methods: From our previous SAGE data-base, Gpnmb (Glycoprotein non-metastatic melanoma protein B) was selected for further analysis. We confirmed the level of mRNA and protein of Gpnmb through RT-PCR, quantitative PCR, and FACS analysis. Then we performed cell-based ELISA and FACS analysis, to know whether there are some molecules which can bind to Gpnmb. Using neutralizing antibody, we blocked the interaction between NK cells and OP9 cells, and checked IFN-${\gamma}$ production by ELISA kit. Results: Gpnmb expression was elevated during in vitro developmental stage and bound to OP9 cells, but not to NK precursor cells. In addition, we confirmed that the levels of Gpnmb were increased at NK precursor stage in vivo. We confirmed syndecan4 as a candidate of Gpnmb's binding molecule. When the interaction between NK cells and OP9 cells were inhibited in vitro, IFN-${\gamma}$ production from NK cells were reduced. Conclusion: Based on these observations, it is concluded that Gpnmb has a potential role in NK cell development from HSCs.

• Clinical and Experimental Reproductive Medicine
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• v.32 no.3
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• pp.217-222
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• 2005

Objectives: We aimed to investigate the clinical effect of low-dose intravenous immunoglobulin treatment in unexplained recurrent spontaneous aborters (RSA) with elevated peripheral CD56+ natural killer (NK) cell levels and to determine the pre-conceptional NK cell percentage predictive of subsequent successful pregnancy outcome. Materials and Methods: Sixty four cases of unexplained recurrent miscarriage with elevated peripheral NK cells (>15%) were received low dose IVIg infusion at the dosage of 400 mg/Kg/month after confirmation of gestational sac and continued until 20 weeks. The patients were divided into two groups according to the pregnancy outcome: Group I was success of treatment defined as live birth at or after 25 gestational weeks and Group II was failure of treatment. The preconceptional levels of the peripheral blood NK cells were compared between two groups. Results: Fifty-three pregnancies resulted in live births after 25 weeks and 11 resulted in abortion (Overall success rate of IVIG treatment was 82.8%). Preconceptional CD56+ NK cell percentage in group II ($27.4{\pm}1.9%$) was higher than those in group I ($22.3{\pm}0.8%$). By using ROC curve, optimal discrimination between success and failure of treatment was achieved with ${\leq}27%$ of preconceptional NK cell percentage. Conclusion: In RSA patients with elevated NK cells, we suggest that preconceptional peripheral blood CD56+ NK cell level could be a useful marker for predicting successful treatment outcome of low-dose IVIg infusion.

• Preventive Nutrition and Food Science
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• v.6 no.3
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• pp.187-191
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• 2001

Effects of kochujang (Korean red pepper soybean paste) extracts on tumor formation, natural killer (NK) cell activity in spleen and glutathione S-transferase (GST) activity in liver were investigated in the sarcoma-180 cell transplanted mice. Inhibitory effects of these samples on lung metastasis of colon 26-M3.1 cells were also evaluated in the Balb/c mice. The injection of methanol extracts from traditional kochujang I (TK I, 0-day fermented), II (TKII, 6-month fermented), commercial kochujang (CK, 1-month fermented) and red pepper powder (RPP) significantly reduced tumor formation in Balb/c mice (p<0.05), TKII decreased tumor growth by 46% compared with control, resulting in the smallest tumor weight. The transplantation of sarcoma-180 cells increased the spleen/body weight ratio of Balb/c mice, while TKI and TKll significantly decreased this index (p<0.05). The effect of TKll and CK, fermented kochujang, on the NK cell activity of splenocytes was higher than that of sarcoma-180 cells transplanted control group. TK II recovered the activity of hepatic GST that was decreased by the transplantation of sarcoma- 180 cells in to the mice. All kochujang-treated mice had significantly fewer lung metastatic colonies than control mice. TKII was the most effective in inhibiting lung metastasis of colon 26-M3.1 cells. These results indicated that optimally ripened (6-month) TK had more suppressive effects on tumor formation and lung metastasis than RPP and kochujang without fermentation and commercially prepared kochujang in mice.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.11-15
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• 2005

Background: Throughtout the last three decades, the therapy of leukemias and lymphoma has set the stage for curative cancer therapy in systemic malignant disease. This was the result of an integrated work of basic reaserch and clinical investigators leading to more aggressive albeit tolerable protocol of chemotherapy and radiotherapy. High dose therapy marks the most elaborated strategies in this field today. However, intensification of conventional therapeutic modalities as mentioned has to be based on new approaches and the exploration of new antineoplastic mechanisms. This insight has resulted in immune therapy of cancer. Among the cells of the immune system, natural killer (NK) cells and T cells are of major interest for the development of therapeutic strategies. Methods: Cytotoxicity to target cells was measured by LDH release method, Characterization of activated lymphocyte was measured by Flow cytometry analysis. Anti-CD3, 16, 56 monoclonal antibody and IL-2 were used for the activation of NK and T cell. The analysis of effect of activated lymphocyte, in vivo, were used by Balb/c nude mouse. Results and Conclusion: Cytotoxicity to K562 cells was significantly higher in the mixture group of NK and T cells than that of a group of activating T cells. The survivors and the rate of reduction of size of tumor craft of nude mouse group treatment with activated lymphocyte was higher than that of the group without treatment with activated lymphocyte. Therefore, this results are suggested that the activated lymphocytes by anti-CD3, CD16 and CD56 can reduce the malignancy effect of lymphoma.