• 대한수의학회지
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• 제26권1호
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• pp.117-124
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• 1986

The present study was undertaken to evaluate rosette formation and NK activity of splenic lymphocytes in 3-methylcholanthrene (MCA) treated mice. Mice were sensitized iv with 0.1ml of 1% sheep red blood cell (SRBC) suspension were treated with a single ip injection of olive oil alone or with different doses of MCA in oil at various time before or after sensitization, and were challenged at 4 days after SRBC. Rosette formation and NK activity of splenic lymphocytes were measured at 24 hours after challenge. Erythrocyte(E) rosette formation of splenic lymphocytes was significantly depressed in mouse treated with large dose of MCA (5~50mg) regardless of injecting time. But, there was no difference in the response between the treated with small dose of MCA (0.5mg). Whereas erythrocyte-antibody(EA) rosette or erythrocyte-antibody-complement(EAC) rosette forming cells were significantly depressed by MCA. Under small dose of MCA (0.5mg), any difference of NK activity was not observed in all course of injecting time. But, under large dose of MCA, the activity was markedly inhibited to about half the values seen in control and this suppression was transient, resulting that the normal level was reached again 19 days after MCA. These results, which conform with the predictions of immunosuppression hypothesis, suggest that MCA inhibits immunological responses including NK activity and thereby allows the outgrowth of antigenic neoplastic cells.

• Journal of Microbiology and Biotechnology
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• 제24권1호
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• pp.127-131
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• 2014

While searching for lactic acid bacteria that can restore aging-impaired immune responses, we isolated the Toll-like receptor (TLR) 2/NF-${\kappa}B$-activating strain Lactobacillus plantarum HY7712 from kimchi and investigated its immunomodulating effect in whole-body ${\gamma}$-irradiated mice. Exposure to HY7712 strongly activated NF-${\kappa}B$ signaling in RAW264.7 cells, but inhibited lipopolysaccharide-stimulated NF-${\kappa}B$ activation. Moreover, HY7712 protected against the downregulation of interferon (IFN)-${\gamma}$ and upregulation of interleukin (IL)-13 caused by ${\gamma}$-irradiation in mice. In mice, ${\gamma}$-irradiation impaired NK-cell activity against YAC-1 tumor cells, but following HY7712 exposure, the activity of NK cells was restored to 91.5% of the level measured in control mice (p < 0.05). These findings suggest that HY7712 activates the TLR2/NF-${\kappa}B$ signaling pathway and protects against the impairment of NK-cell activity caused by ${\gamma}$-irradiation or aging.

• Clinical and Experimental Reproductive Medicine
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• 제37권2호
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• pp.115-124
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• 2010

목 적: 임신 전 $CD3^-/CD56^+/CD16^+$ 말초혈액 자연살해세포 (pbNK cell)의 분획과 세포용해 활성도를 정상군과 습관성 유산의 기왕력을 가진 환자군으로 나누어 비교, 분석하고 습관성 유산의 위험도를 제시할 수 있는 각각의 cut-off value를 설정하고자 하였다. 연구방법: 전향적 연구로서 습관성 유산의 기왕력이 있는 여성을 환자군 (n=35)으로 하였으며, 대조군으로 불임이나 습관성 유산의 기왕력이 없으며 정상아의 출산 경험이 있는 여성을 대조군 (n=15)으로 설정하였다. 유세포분석기를 이용하여 pbNK cell 분획 및 세포용해 활성도를 측정 후 그 결과를 비교 분석하였다. 결 과: pbNK cells의 분획은 습관성 유산 환자군에서 대조군에 비해 통계적으로 유의하게 높은 결과를 보였다($14.2{\pm}5.2$ vs. $9.4{\pm}3.7%$, p=0.002, 95% confidence interval [CI] 1.8~7.8). Receiver operating characteristic curve (ROC) 곡선을 이용하여 pbNK cell의 분획에 대한 cut-off values을 12.1%로 정하였을 때 습관성 유산의 위험도는 8.4배 증가하였다. pbNK cell의 K562 세포용해 활성도를 3가지 다른 Effector to Target (E:T) 비율 (50:1, 25:1, 12.5:1)을 사용하여 측정한 결과 각각의 경우에 있어 습관성 유산 환자군에서 대조군에 비해 통계적으로 유의하게 증가된 결과를 보였다 ($48.3{\pm}19.0$ vs. $31.3{\pm}11.9%$ in 50:1 ratio, p=0.002; $37.0{\pm}18.1$ vs. $20.2{\pm}9.2%$ in 25:1 ratio, p<0.001; $23.5{\pm}12.7$ vs. $12.4{\pm}7.3%$ in 12.5:1 ratio, p=0.001). ROC 곡선을 이용하여 각각 E:T 비율에서 세포용해 활성도의 cut-off values (43.1% in 50:1, 26.9% in 25:1, and 17.4% in 12.5:1)을 설정하여 분석한 결과 습관성 유산의 위험도는 각각 10.0배, 11.4배, 그리고 15.0배 증가된 결과를 보였다. 결 론: 원인이 분명하지 않은 습관성 유산 환자에서 pbNK cell의 분획과 세포용해 활성도를 측정하는 것은 면역학적 원인, 특히 동종면역 요인에 의한 습관성 유산의 유용한 진단 지표로 이용될 수 있을 것으로 사료된다. 향후 동종 면역반응에 의한 습관성 유산 환자에서 면역학적 원인의 치료 전, 후 pbNK cell의 분획과 세포용해 활성도를 측정, 비교하여 그 효과를 증명하는 연구가 필요할 것으로 생각된다.

• 약학회지
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• 제54권3호
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• pp.192-199
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• 2010

Colorectal cancer is one of the most common alimentary malignancies. In this study, the antitumor activity of activated human natural killer (NK) cells against human colorectal cancer was evaluated in vivo. Human NK cells are the key contributors of innate immune response and the effective functions of these cells are enhanced by cytokines. Human peripheral blood mononuclear cells (PBMC) were cultured with interleukin-2 (IL-2)-containing medium for 14 days and resulted in enriched NK cell population. The resulting populations of the cells comprised 7% $CD3^+CD4^+$ cells, 25% $CD3^+CD8^+$ cells, 13% $CD3^-CD8^+$ cells, 4% $CD3^+$CD16/$CD56^+$ cells, 39% $CD3^+$CD16/$CD56^-$ cells, and 52% $CD3^-$CD16/$CD56^+$ cells. Tumor necrosis factor alpha (TNF-$\alpha$), interferon gamma (IFN-$\gamma$), IL-2, IL-4, and IL-5 transcripts of the activated NK cells were confirmed by RT-PCR. In addition, activated NK cells at doses of 2.5, 5 and 10 million cells per mouse inhibited 10%, 34% and 47% of SW620-induced tumor growth in nude mouse xenograft assays, respectively. This study suggests that NK cell-based immunotherapy may be used as an adoptive immunotherapy for colorectal cancer patients.

• Journal of Ginseng Research
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• 제46권2호
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• pp.304-314
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• 2022

Background: Ginsenosides are biologically active components of ginseng and have various functions. In this study, we investigated the immunomodulatory activity of a ginseng product generated from ginseng powder (GP) via enzymatic bioconversion. This product, General Bio compound K-10 mg solution (GBCK10S), exhibited increased levels of minor ginsenosides, including ginsenoside-F1, compound K, and compound Y. Methods: The immunomodulatory properties of GBCK10S were confirmed using mice and a human natural killer (NK) cell line. We monitored the expression of molecules involved in immune responses via enzyme-linked immunosorbent assay, flow cytometry, NK cell-targeted cell destruction, quantitative reverse-transcription real-time polymerase chain reaction, and Western blot analyses. Results: Oral administration of GBCK10S significantly increased serum immunoglobulin M levels and primed splenocytes to express pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α, and interferon-γ. Oral administration of GBCK10S also activated NK cells in mice. Furthermore, GBCK10S treatment stimulated a human NK cell line in vitro, thereby increasing granzyme B gene expression and activating STAT5. Conclusion: GBCK10S may have potent immunostimulatory properties and can activate immune responses mediated by B cells, Th1-type T cells, and NK cells.

• Asian Pacific Journal of Cancer Prevention
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• 제14권1호
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• pp.309-314
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• 2013

Aim: Brain tumors almost universally have fatal outcomes; new therapeutics are desperately needed and will only come from improved understandins of glioma biology. Methods: Exosomes are endosomally derived 30~100 nm membranous vesicles released from many cell types. Examples from GL26 cells were here purified using density gradient ultracentrifugation and monitored for effects on GL26 tumor growth in C57BL/6j mice (H-2b). Lactate dehydrogenase release assays were used to detect the cytotoxic activity of CD8+T and NK cells. Percentages of immune cells producing intracellular cytokines were analyzed by FACS. Results: In this study, exosomes from murine-derived GL26 cells significantly promoted in vivo tumor growth in GL26-bearing B6 mice. Then we further analyzed the effects of the GL26 cells-derived exosomes on immune cells including CD8+T, CD4+T and NK cells. Inhibition of CD8+T cell cytotoxic activity was demonstrated by CD8+T cell depletion assays in vivo and LDH release assays in vitro. The treatment of mice with exosomes also led to a reduction in the percentages of CD8+T cells in splenocytes as determined by FACS analysis. Key features of CD8+T cell activity were inhibited, including release of IFN-gamma and granzyme B. There were no effects of exosomes on CD4+T cells and NK cells. Conclusion: Based on our data, for the first time we demonstrated that exosomes from murine derived GL26 cells promote the tumor growth by inhibition of CD8+T cells in vivo and thus may be a potential therapeutic target.

• 생약학회지
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• 제25권4호통권99호
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• pp.348-355
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• 1994

An antitumor component, F-D-P, was purified from the hot water extract of the carpophores of Elfvingia applanata by precipitation with ethanol, dialysis, and passage through a column of DEAE-cellulose ion exchange. F-D-P inhibited the growth of Sarcoma 180 in mice showing the tumor inhibition ratio of 88.3% in doses of 20 mg/kg for ten days. Chemical analysis of F-D-P showed that it was composed of polysaccharide(65.3%) and protein(6.5%0, and that the monosaccharides consisting of the polysaccharide was glucose(89.1%) and mannose(10.9%). The immunomodulatory activities of F-D-P were explored by determining its effect on the proliferation of the whole and subpopulations of lymphocytes, and on the generation of natural killer(NK) cell activity in vitro. F-D-P was mitogenic to total lymphocytes and B cells, but not to purified T cells, even in the presence of accessory cells. F-D-P did not increase NK cell activity when added to cultures of resting lymphocytes. From these results, it is clear that F-D-P modulates primarily the humoral immune responeses.

• 한국식품영양과학회지
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• 제26권6호
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• pp.1194-1199
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• 1997

The effect of hot taste preference on selected immune responses was investigated in human peripheral immunocompetent cells. Human lymphocytes and natural killer(NK) cells were prepared at a concentration of 2$\times$$10^{6}$ cells/ml in RPMI-1640 containing 10% fetal bovine serum. Lymphocytes proliferation was determined with the [$^{3}H$]-thymidine pulse for 18hrs after concanavalin A, phytohemagglutinin, Salmonella typhimurium mitogen, or media alone. NK cell activity was measured by cytolysis of $^51Cr$-labeled target cells K562. Serum antibodies levels such as IgM, IgG, IgA were also measured by ELISA method. There was no difference of serum IgM level among the groups, but IgG and IgA levels were greater in the group with hot taste preference than those of the group without hot taste preference. In lymphocytes of the group with hot taste preference there was a greater mitogen-induced lymphocyte proliferative responses compared to the group without hot taste preference. In addition, NK cell activity in group with hot taste preference was lower than that of the group without hot taste preference. These results suggest that the eating habit of spicy food containing hot components may affect immune status by modulating selective immunocompetent cells function.

• 생약학회지
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• 제30권2호
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• pp.115-122
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• 1999

In order to investigate the effects of Bupleuri Radix aqua-acupuncture solution (BRAS) on immuno suppression induced by glucocorticoid, ICR mice were administrated with glucocorticoid (80 mg/kg) for 7 days, and immunized with hapten, methamphetamine-horseradish peroxidase $(10\;{\mu}g/mouse)$. And then, BRAS (0.2ml/mouse) injected into $CV_4\;and\;BL_{23}$, which are the classical acupuncture points in traditional medicine, for 7 days. And then B and T cells proliferation and cytolytic activity of natural killer (NK) cells were measured. Intraperitoneal injection of glucocorticoid decreased lysozyme activity in macrophage and cytolytic activity of NK cell. B and T cell proliferation were significantly increased in aqua-acupuncture group compared to normal group. On the other hand, BRAS significantly increased the lysozyme activity in macrophage, and the cytolytic activity of purified NK cell on K562. These results suggest that BRAS at $CV_4\;and\;BL_{23}$ may proliferate B and T cells that are suppressed by glucocorticoid and activate NK cell activity.

• Nutrition Research and Practice
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• 제11권1호
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• pp.43-50
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• 2017

BACKGROUND/OBJECTIVES: The present study investigated the hypothesis that a highly pure linear ${\beta}$-1,3-glucan produced by Agrobacterium sp. R259 enhances human natural killer (NK) cell activity and suppresses pro-inflammatory cytokines. SUBJECTS/METHODS: In an eight-week, double-blind, randomized, placebo-controlled clinical trial, 83 healthy adults with white blood cell counts of $4,000-8,000cells/{\mu}L$ were participated and randomly assigned to take two capsules per day containing either 350 mg ${\beta}$-1,3-glucan or placebo. Six participants withdrew their study consent or were excluded due to NK cell activity levels outside the normal range. NK cell activity and serum levels of immunoglobulin G (IgG) and cytokines, such as interferon (IFN)-${\gamma}$, interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and tumor necrosis factor (TNF)-${\alpha}$ were measured. RESULTS: NK cell activity and the serum levels of IL-10 were significantly higher from baseline to week 8 in the ${\beta}$-glucan group compared with the placebo group (P = 0.048, P = 0.029). Consumption of ${\beta}$-1,3-glucan also significantly increased NK cell activity compared with placebo after adjusting for smoking and stress status (P = 0.009). In particular, the effect of ${\beta}$-1,3-glucan on NK cell activity was greater in participants with severe stress than in those experiencing mild stress. However, the administration ${\beta}$-1,3-glucan did not significantly modulate the levels of IFN-${\gamma}$, IL-2, IL-4, IL-6, IL-12, TNF-${\alpha}$ and IgG compared with the placebo. CONCLUSION: The results showed that supplementation with bacterial ${\beta}$-1,3-glucan significantly increased NK cell activity without causing any adverse effects. Additionally, the beneficial effect of ${\beta}$-1,3-glucan on NK cell activity was greater in participants experiencing severe stress.