• 한국식품영양과학회지
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• 제45권11호
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• pp.1564-1570
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• 2016

본 연구에서는 고순도 ${\beta}$-1.3/1.6-glucan이 선천면역계에 중요한 역할을 하는 대식세포와 자연살해세포의 활성화와 적응면역계에서 중요한 역할을 하는 T 세포 면역계에 대한 면역조절 효과를 살펴보고자 대식세포의 활성능, 자연살해 세포의 활성능, 그리고 T 세포 면역계에 조절작용을 하는 사이토카인, CD4+/CD8+ T 세포에 미치는 영향을 관찰하였다. 마우스 복강에서 불리한 대식세포를 이용하여 세포독성을 확인한 결과 고순도 ${\beta}$-1.3/1.6-glucan $10{\sim}200{\mu}g/mL$의 농도에서 독성이 나타나지 않았다. 또한, 고순도 ${\beta}$-1.3/1.6-glucan은 대식세포의 활성능, 자연살해세포의 활성능에 도움을 주어 활성능을 증가시켜 외부로부터 침입한 미생물, 감염된 세포나 종양세포 등을 효과적으로 제거할 수 있을 것이라 예상할 수 있었다. 마지막으로 T 세포 면역계에 조절작용을 하는 사이토카인과 CD4+/CD8+를 확인한 결과 고순도 ${\beta}$-1.3/1.6-glucan이 사이토카인들의 분비량 및 CD4+/CD8+를 증가시켜 T 세포 면역계에 조절뿐아니라 B 세포 면역계의 조절에 도움을 줄 것이라 예상할 수 있었다. 결론적으로 고순도 ${\beta}$-1.3/1.6-glucan은 선천면역뿐 아니라 적응면역에서 영향을 미칠 것이라 생각하며 면역조절에 긍정적인 변화를 보였으므로 추후 면역 조절제로서 기능성 식품의 상업화에 기초 자료가 되어 국내 기능성 소재로서의 개발 가능성을 기대할 수 있다.

• 한국식품영양과학회지
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• 제41권4호
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• pp.494-500
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• 2012

본 연구에서는 면역억제 동물모델에서 밀리타리스 동충하초 50% 에탄올 추출물의 면역력 증강 기능을 평가하였다. 이를 위하여 C57BL/6 마우스에 cyclophosphamide를 2회 복강주사 하여 면역력을 억제한 후, 밀리타리스 동충하초 추출물을 30, 100, 300 mg/kg 용량으로 12일간 경구투여 하였다. 마우스를 희생하여 몸무게 및 면역장기 무게, 비장세포의 증식, 비장세포의 cytokine 분비능, NK 세포 활성을 측정하였다. 그 결과, cyclophosphamide 투여에 의한 면역억제는 마우스의 몸무게와 간의 무게에 영향을 주지 않았으나 흉선의 무게는 감소시켰고 비장의 무게는 증가시켰다. 밀리타리스 동충하초 추출물 투여는 마우스의 몸무게 및 면역장기 무게에 영향을 주지 않았다. Cyclophosphamide 투여는 비장세포의 증식능을 감소시켰으며 밀리타리스 동충하초 추출물은 용량 의존적으로 비장세포 증식을 증가시켜 실험에 사용한 전 용량에서 비장세포의 유의적인 증식효과를 보였다. 비장세포의 cytokine 분비능을 측정한 결과, 밀리타리스 동충하초 추출물 투여는 IL-2, IL-12, IFN-${\gamma}$, TNF-${\alpha}$ 같은 Th1 cytokine의 분비를 대조군에 비해 유의적으로 증가시켰으나, IL-4와 IL-10 같은 Th2 cytokine의 분비에는 영향을 미치지 않았다. 또한 cyclophosphamide는 NK 세포의 활성을 정상군에 비하여 유의적으로 감소시켰으며, 밀리타리스 동충하초 추출물 투여는 cyclophosphamide에 의해 저하된 NK 세포 활성을 현저하게 증가시켰다. 이상의 결과를 종합해 볼 때, 밀리타리스 동충하초는 면역력이 억제된 상황에서 면역력을 증강시키며, 이러한 면역력 증강 효과는 체액성 면역보다 세포성 면역력 증강에 기인하는 것으로 보인다.

• Journal of Microbiology and Biotechnology
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• 제25권7호
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• pp.1036-1046
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• 2015

Extracts from Asian medicinal herbs are known to be successful therapeutic agents against cancer. In this study, the effects of three types of herbal extracts on anti-tumor growth were examined. Among the three types of herbal extracts, H9 showed stronger anti-tumor growth effects than H5 and H11 in vivo. To find the molecular mechanism by which H9 inhibited the proliferation of breast cancer cell lines, the levels of apoptotic markers were examined. Proapoptotic markers, including cleaved PARP and cleaved caspases 3 and 9, were increased, whereas the anti-apoptotic marker Bcl-2 was decreased by H9 treatment. Next, the combined effect of H9 with the chemotherapeutic drugs doxorubicin/cyclophosphamide (AC) on tumor growth was examined using 4T1-tumor-bearing mice. The combined treatment of H9 with AC did not show additive or synergetic anti-tumor growth effects. However, when tumor-bearing mice were co-treated with H9 and the targeted anti-tumor drug trastuzumab, a delay in tumor growth was observed. The combined treatment of H9 and trastuzumab caused an increase of natural killer (NK) cells and a decrease of myeloid-derived suppressor cells (MDSC). Taken together, H9 induces the apoptotic death of tumor cells while increasing anti-tumor immune activity through the enhancement of NK activity and diminishment of MDSC.

• 한국식품과학회지
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• 제51권2호
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• pp.152-159
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• 2019

전통발효식초에 속하는 사과식초로부터 에탄올 및 증류수를 이용, 다당체를 분리하여 새로운 면역활성 물질을 확인하고자 하였다. 사과식초를 농축하고, 80% 에탄올을 가하여 침전물을 얻었으며 소량에 물에 용해하여 투석 및 동결건조를 거쳐 조다당 KAV-0를 얻었다. 구성당 분석 결과, KAV-0는 주로 mannose 38.2%, galactose 19.1% 및 glucose 14.3%로 구성되어있음을 확인하였고, 정상세포주(RAW 264.7 세포 및 대식세포) 및 종양세포주(B16-BL6 melanoma 세포)에 대해 세포독성 측정 결과, 직접적인 세포독성을 나타내지 않았다. 대식세포 유래 세포주인 RAW 264.7 세포 자극에 대한 사이토카인 및 산화질소 생산능을 측정한 결과, IL-6, $TNF-{\alpha}$ 및 산화질소 모두 농도 의존적으로 분비능이 증가하고 저농도에서도 우수한 활성을 나타냈으며, 마우스 복강유래 대식세포 자극에 대한 사이토카인 및 산화질소 생산능에서도 동일한 양상의 결과를 보여 사과식초 유래 조다당 KAV-0가 높은 대식세포 활성능을 소유함을 확인할 수 있었다. 한편, KAV-0의 정맥투여에 따른 NK 세포 활성화를 측정한 결과(ex vivo), 시료에 의해 활성화된 NK 세포는 Yac-1 종양 세포주에 대한 치사활성을 농도 의존적으로 증진시켰으며, $1,000{\mu}g/mouse$에서 월등히 우수한 NK 세포 활성능을 유도하였다. 또한, B16-BL6 melanoma를 이용한 폐암전이모델에서 KAV-0를 정맥투여한 뒤 항전이 활성을 측정한 결과, 농도 의존적으로 암 저해 효과가 나타났으며, 특히 $1,000{\mu}g/mouse$에서는 약 53%의 우수한 암전이 억제 활성을 나타냈다. 이상의 결과로부터 사과식초 유래 조다당 KAV-0는 인체의 면역계를 자극하여 우수한 면역활성 및 항전이 효과를 나타낼 수 있음이 확인되었고 건강 기능성 소재로의 활용 가능성이 충분할 것으로 최종 판단되었다.

• 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.

• 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.

• Molecules and Cells
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• 제42권12호
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• pp.869-883
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• 2019

Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL-15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancer-cell vaccine using mitomycin C (MMC)-treated IL-15:IL-15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) long-term protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4⁺ T, CD8⁺ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.

• 대한한방내과학회지
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• 제29권4호
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• pp.1075-1082
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• 2008

Objectives : The purpose of this experiment is comparing the difference on natural killer cell activity through Korean red ginseng and Chinese red ginseng by $^{51}Cr$ release assay. Methods : Thirty rats were equally divided into a Korean red ginseng group, a Chinese red ginseng group and a control group. Korean and Chinese red ginseng were administrated to the rats at 200mg daily for a weak, while 0.9% normal saline was given to the control. Percent specific lysis (PSL) and lytic units (LU) were calculated from spleen cells by $^{51}Cr$ release assay. Results : Percent specific lysis of the Korean red ginseng group was significantly higher than that of the control in the ratio of 100:1, effector cell:target cell (p<0.05). Percent specific lysis of Korean red ginseng group was also significantly higher than that of the Chinese red ginseng group in the ratio of 25:1, effector cell:target cell (p<0.05). Chinese red ginseng showed no effect on NK cell activity. Conclusions : These findings suggest that Korean red ginseng improves immunologic function and shows superior effects than Chinese red ginseng.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Signal transduction in Toxicology
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• pp.114-114
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• 2001

Di-n-butyl phthalate (DBP) is not only a plasticizer and solvent used in industry but also one of endocrine disruptor chemicals, a low level contaminant found in a wide variety of different media ranging from drinking water to infant formulae. To evaluate the cytotoxic function of NK cells in mice after contact with DBP, C57BL/6 female mice were orally dosed with di-n-butyl phthalate (250, 500, or 750 mg/kg body weight) for 14 consecutive days, and the control mice were administered vehicle (corn oil).(omitted)

• Molecular & Cellular Toxicology
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• 제5권1호
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• pp.93-98
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• 2009

Stephania delavayi Diels. has been used as an immune activator or an anti-inflammatory drug in China. We examined the immune modulation effect and 7-days repeated-dose toxicity to validate its biological safety and efficiency. Mice were repeatedly administrated with 50 mg/kg S. delavayi Diels. daily by I.P for 7 days. S. delavayi Diels. induced B cell activation but had no effect on other immune cells such as T cell, natural killer (NK) cell, and macrophage ($M{\varphi}$). S. delavayi Diels.-treated group exhibited no statistical significance from the control group in physical conditions; body weight, complete blood count (CBC), serum biochemical indexes etc. There was no difference between the control group and S. delavayi Diels.-treated group in gross findings such as histopathological alteration. In conclusion, S. delavayi Diels. is safe above the dose of immune modulation.