• Reproductive and Developmental Biology
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• 제41권3호
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• pp.57-63
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• 2017

Xenotransplantation is proposed as a solution to the problem of organ shortage. However, transplantation of xenogeneic organs induces an antigen-antibody reaction in ${\alpha}$-1,3-gal structure that are not present in humans and primates, and thus complement is also activated and organs die within minutes or hours. In this study, we used FasL gene, which is involved in the immune response of NK cell, and US11, which suppresses MHC Class I cell membrane surface expression, to inhibit cell mediated rejection in the interspecific immunity rejection, and also hDAF(CD55) was introduced to confirm the response to C3 complement. These genes were tranfeced into Korean native pig fetal fibroblasts using pCAGGS vector. And cytotoxicity of NK cell and human complement was confirmed in each cell line. The US11 inhibited the cytotoxicity of NK cell and, in addition, the simultaneous expression of US11 and Fas ligand showed excellent suppress to T-lymphocyte cytotoxicity, hDAF showed weak resistance to cytotoxicity of natural killer cell but not in CD8+ CTLs. Cytotoxicity study with human complement showed that hDAF was effective for reducing complement reaction. In this studies have demonstrated that each gene is effective in reducing immune rejection.

• 대한약침학회지
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• 제6권1호
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• pp.76-94
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• 2003

Objectives : The purpose of this study was to investigate Acute$\cdot$Subacute Toxicity and Anti-cancer Effect of K-Herbal-acupuncture in mice and rats. Methods : Balb/c mice were injected intraperitoneally with K-herbal-acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were injected intraperitoneally with K-herbal-acupuncture for subacute toxicity test. K-Herbal-acupuncture was injected on abdomen of mice with S-180 cancer cell line. Result : 1. $LD_{50}$ of K-Herbal-acupuncture was limited $4{\times}10^{-3}$ml/kg~$2{\times}10^{-3}$ml/kg by the test. 2. In acute toxicity test, all of mice were down to the moving reflex, but the weight of mice was increased in treatment group, compared with the normal group. (P<0.05) 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment II group, total cholesterol was increased both treatments.(P<0.05) 4. In subacute toxicity test, the clinical signs of toxication was down to the moving reflex, but it is not severe like acute toxicity test, and observed weight loss at the treatments. 5. In subacute toxicity test, liver weight was decreased compared with the normal group. (P<0.05) 6. In subacute toxicity test of complete blood count test (CBC) of rat, HCT was decreased in treatments, compared with the normal group.(P<0.05) 7. In subacute toxicity test of serum biochemical values of rat, uric acid and triglyceride were decreased, and glucose was increased in treatment groups compared with the control group. (P<0.05) 8. Median survival time was increased about $45\%$ in treatment groups compared with the control group.(P<0.05) 9. Natural killer cell activity was increased in B16F10 lung cancer model, but it was not in sarcoma-180 abdomen cancer. 10. In interleukin-2 productivity test, treatment groups didn't show significant change in lung cancer and abdomen cancer, compared with the normal group.(P<0.005) 11. In making an examination of metastatic cancer with the naked eye, melanoma metastasized in the Lung of C57BL/6 mice. The treated group showed more Melanoma than the control in the numbers and volume. Conclusion : According to the result, K-herbal-acupuncture need further study to know the function and effect in cancer.

• 대한한방종양학회지
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• 제2권1호
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• pp.75-90
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• 1996

This experiment was designed to study the antitumor effects and Activity of Natural Killer Cell of semen Tiglii plus Rhizoma Rhei. The cytotoxic and antitumor effects were evaluated on human cell lines(A549, Caki-1, LL2, Sarcoma 180, NIH/3T3) after exposure to prebrewed Semen Tiglii plus Rhizoma Rhei water extract 0.1, 0.2, 0.4, 0.8, 1.6mg/ml using in MTT assay, LDH, colony forming efficency and SRB assay which were regarded as a valuable method for cytotoxic and antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows. 1. From the result of MTT assay, the cytotoxicity of ST(生巴豆霜), ST+RR(生巴豆霜加大黃) were concentration-dependently increased in both group of the ST and ST+RR, the cytotoxicity of ST+RR(生巴豆霜加大黃) was similar to that of ST(生巴豆霜). 2. From the result of LDH, the cytotoxicity of ST, ST +RR were concentrati -on-dependently increased in both group of the ST and ST+RR, the cytotoxicity of ST+RR was similar to that of ST. 3. The antitumor effect on A549 tumor cell from the result of colony forming efficiency showed the inhibitory effect on the growth in both group of the ST and ST+RR, the inhibitory effect on growth was low slightly in the ST+RR. 4. From the result of SRB assay, the antitumor effect on caki-1 tumor cell of ST, ST+RR showed the inhibitory effect on the growth in both group of the ST and ST+RR, the antitumor effect of ST+RR was similar to that of ST. 5. Median survival time and increased life span were increased slightly in both group of the ST and ST+RR. 6. The inhibitory effect on the growth of Sarcoma 180 and Lewis lung carcinoma tumor cell were increased slightly in both group of the ST and ST+RR. 7. The activity of NK cell was increased in the ST+RR.

• IMMUNE NETWORK
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• 제3권3호
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• pp.188-200
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• 2003

Background: Immunization of dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL) that are responsible for protection and regression. In this study, we examined whether the uptake of necrotic tumor cells could modulate DC phenotypes and whether the immunization of necrotic tumor cell-loaded DCs could elicit efficient tumor specific immune responses followed by a regression of established tumor burdens. Methods: We prepared necrotic tumor cell-pulsed DCs for the therapeutic vaccination and investigated their phenotypic characteristics, the immune responses induced by these DCs, and therapeutic vaccine efficacy against colon carcinoma in vivo. Several parameters including phagocytosis of tumor cells, surface antigen expression, chemokine receptor expression, IL-12 production, and NK as well as CTL activation were assessed to characterize the immune response. Results: DCs derived from mouse bone marrow efficiently phagocytosed necrotic tumor cells and after the uptake, they produced remarkably increased levels of IL-12. A decreased CCR1 and increased CCR7 expression on DCs was also observed after the tumor uptake, suggesting that antigen uptake could induce DC maturation. Furthermore, co-culturing of DCs with NK cells in vitro enhanced IL-12 production in DCs and IFN-${\gamma}$ production in NK cells, which was significantly dependent on IL-12 production and cell-to-cell contact. Immunization of necrotic tumor cell-loaded DCs induced cytotoxic T lymphocytes as well as NK activation, and protected mice against subsequent tumor challenge. In addition, intratumoral or contra-lateral immunization of these DCs not only inhibited the growth of established tumors, but also eradicated tumors in more than 60% of tumor-bearing mice. Conclusion: Our data indicate that production of IL-12, chemokine receptor expression and NK as well as CTL activation may serve as major parameters in assessing the effect of tumor cell-pulsed DC vaccine. Therefore, DCs loaded with necrotic tumor cells offer a rational strategy to treat tumors and eventually lead to prolonged survival.

• Genomics & Informatics
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• 제14권3호
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• pp.78-84
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• 2016

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.

• 대한본초학회지
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• 제32권5호
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• pp.27-38
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• 2017

Objective : In the present study, we examined whether Canavalia gladiata D.C. (CG) and Arctium lappa L., Redix (AL) mixture (CGAL), their components, lupeol and chicoric acid, regulate immune system and suppress the tumor in vitro and in vivo. Methods : LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) were measured after treatment with CG extract (CGE), CGAL, lupeol, chicoric acid and lupeol and chicoric acid mixture (lupeol+CA) in Raw264.7 cell. To determine the effect of CGE on immune responses, immune cell population and IgG production were assessed in mice. To investigate the effect of CGAL and their component on anti-tumor activity, tumor volume and weight were measured, cell cycles and immune cell population were analyzed in MC38 injected tumor bearing mice. Also, NK cell activity was determined in splenocyte isolated from tumor bearing mice. Results : CGE, CGAL, lupeol, chicoric acid and lupeol+CA decreased the LPS-induced ROS and NO production without cell toxicity in RAW264.7 cells. CGE increased the immune cell populations of $CD4^+T$, $CD8^+T$ and macrophages in various immune organ of mice. In tumor bearing mice, CGAL, lupeol, chicoric acid and lupeol+CA suppressed tumor volume and weight. In cell cycle analysis, they decreased the percentages of S phase. In addition, CGAL, lupeol, chicoric acid and lupeol+CA immune cell populations of $CD4^+T$, $CD8^+Tcell$, NK cell and macrophage in tumor as well as NK cell activity. Conclusion : CGAL and its compounds may enhance immune responses and suppress tumor growth, and may be capable of developing health functional foods.

• 분석과학
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• 제27권5호
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• pp.248-253
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• 2014

이 연구는 Mn과 Pb의 노출이 면역체계에 미치는 영향을 파악하고자 하였다. 연구대상자는 남성 근로자 42 명으로, 대상자 중 13명은 사무직 근로자(실험군 I), 21 명은 제조업 사업장 근로자(실험군 II), 8명은 용접 작업자(실험군 III)였다. 대상자의 혈액 중 Mn과 Pb 농도는 실험군별로 유의한 차이를 보였다. 실험군 I 대상자의 CD19+와 total lymphocytes 농도는 기타의 실험군 대상자에서보다 유의하게 높았으나 다른 T lymphocytes subpopulation의 농도는 차이가 없었다. Mn과 Pb 농도는 T lymphocytes subpopulation과 음의 상관관계를 보였으나, Mn은 CD4+CD45RO+와 자연살해세포를 제외한 T lymphocytes subpopulation과 유의한 음의 상관관계를 보였다. Pb 농도는 단지 total lymphocytes 농도와 유의한 음의 상관관계를 보였다. 이 연구에서 Mn과 Pb의 직업적인 노출은 세포성면역계에 영향을 미칠 수 있음을 제시하였다.

• Journal of Ginseng Research
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• 제33권4호
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• pp.278-282
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• 2009

본 논문은 홍삼 산성 다당류 (RGAP)의 생체외 쥣과 NK 세포 활성 향상에 대한 내용으로 주요 내용은 다음과 같다. RGAP는 Yac-1 종양 세포에서 NK 세포 활성을 향상시켰다. 비장 세포에 16시간 동안 RGAP 10 및 $100{\mu}g$/ml을 처리한 결과, NK 활성이 239와 250% 증가 하였다. 인터페론 (IFN)-$\gamma$ 생성은 17-125% 증가하였고, 종양 괴사 인자 (TNF)-${\alpha}$ 생성도 15-100% 증가 하였다. NK 세포의 세포 독성 증가는 NK 세포가 생성하는 이 두 시토카인 증가가 원인이다. 따라서 RGAP는 NK 세포에 미치는 면역증진 효과가 있다는 내용이다.

• 생명과학회지
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• 제29권7호
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• pp.817-823
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• 2019

노화는 광범위한 생리 변화이다. 노화가 진행됨에 따라 면역반응은 쇠퇴하고 조절장애가 나타나는데 이를 포괄적 의미로 immunosenescense라고 정의한다. 내재면역반응과 적응면역 반응 모두의 면역 성분은 노화가 진행됨에 따라 영향을 받아 감염성 질병에 대한 취약성이 증가하게 된다. 노화된 동물 모델과 인간에서 면역 세포의 수와 용해성 면역 인자의 양이 줄어 들었고, 면역체계의 기능이 감소하였고, 구조적인 변형과 퇴화가 나타났다. 또한, 세포 내 신호분자와 같은 내재적 변화도 발견되었다. 최근 노화와 관련된 연구는 급격히 증가하였고, 면역체계 영역을 포함하여 다양한 방향으로 노화현상을 분석하는 진보된 기술들이 개발되고 있다. 이 총설은 면역의 주요 구성 요소의 노화 관련 변화에 대한 광범위한 개요를 제공하고자 하였다.

• IMMUNE NETWORK
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• 제20권6호
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• pp.51.1-51.17
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• 2020

Respiratory syncytial virus (RSV) causes severe pulmonary disease in infants, young children, and the elderly. Formalin inactivated RSV (FI-RSV) vaccine trials failed due to vaccine enhanced respiratory disease, but the underlying immune mechanisms remain not fully understood. In this study, we have used wild type C57BL/6 and CD4 knockout (CD4KO) mouse models to better understand the roles of the CD4 T cells and cellular mechanisms responsible for enhanced respiratory disease after FI-RSV vaccination and RSV infection. Less eosinophil infiltration and lower pro-inflammatory cytokine production were observed in FI-RSV vaccinated CD4KO mice after RSV infection compared to FI-RSV vaccinated C57BL/6 mice. NK cells and cytokine-producing CD8 T cells were recruited at high levels in the airways of CD4KO mice, correlating with reduced respiratory disease. Depletion studies provided evidence that virus control was primarily mediated by NK cells whereas CD8 T cells contributed to IFN-γ production and less eosinophilic lung inflammation. This study demonstrated the differential roles of effector CD4 and CD8 T cells as well as NK cells, in networking with other inflammatory infiltrates in RSV disease in immune competent and CD4-deficient condition.