• IMMUNE NETWORK
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• 제9권4호
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• pp.115-121
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• 2009

Natural killer (NK) cells play key roles in innate and adaptive immune defenses. NK cell responses are mediated by two major mechanisms: the direct cytolysis of target cells, and immune regulation by production of various cytokines. Many previous reports show that the complex NK cell activation process requires de novo gene expression regulated at both transcriptional and post-transcriptional levels. Specialized un-translated regions (UTR) of mRNAs are the main mechanisms of post-transcriptional regulation. Analysis of posttranscriptional regulation is needed to clearly understand NK cell biology and, furthermore, harness the power of NK cells for therapeutic aims. This review summarizes the current understanding of mRNA metabolism during NK cell activation, focusing primarily on post-transcriptional regulation.

• 대한의생명과학회지
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• 제29권4호
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• pp.382-385
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• 2023

NK (Natural killer) cells are innate immune cells and play important roles as the first immune cells to act when cancer occurs. In many cancer patients, NK cells can be seen to be inactivated, suggesting that NK cells are important in cancer treatment. In order to overcome the disadvantages of NK cells in cancer treatment, it is critical to develop strategies that enhance the proliferation and cytolytic function of NK cells. We applied niclosamide to measure the degree of NK cell activation, and obtained unexpected results of increased NK cell numbers and anti-tumor activity. Although further investigation is required to uncover the detailed mechanisms, our results suggest that Niclosamide is a promising candidate to increase the efficacy of cancer immunotherapy using NK cells.

• International Journal of Molecular Medicine
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• 제44권5호
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• pp.1641-1652
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• 2019

Conditioned media from various sources comprise numerous growth factors and cytokines and are known to promote the regeneration of damaged tissues. Among these, natural killer cell conditioned medium (NK-CdM) has been shown to stimulate collagen synthesis and the migration of fibroblasts during the wound healing process. With a long-term aim of developing a treatment for skin photoaging, the ability of NK-CdM to prevent ultraviolet-B (UV-B) damage was assessed in neonatal human dermal fibroblasts (NHDFs) and an in vitro reconstructed skin model. The factors present in NK-CdM were profiled using an antibody array analysis. Protein and mRNA levels in UV-B exposed NHDFs treated with NK-CdM were measured by western blotting and quantitative reverse transcription-PCR, respectively. The total antioxidant capacity of NK-CdM was determined to assess its ability to suppress reactive oxygen species. The anti-photoaging effect of NK-CdM was also assessed in a 3D reconstituted human full skin model. NK-CdM induced proliferation of UV-B-treated NHDFs, increased procollagen expression, and decreased matrix metalloproteinase (MMP)-1 expression. NK-CdM also exhibited a potent antioxidant activity as measured by the total antioxidant capacity. NK-CdM inhibited UV-B-induced collagen degradation by inactivating MAPK signaling. NK-CdM also elicited potential anti-wrinkle effects by inhibiting the UV-B-induced increase in MMP-1 expression levels in a 3D reconstituted human full skin model. Taken together, the suppression of both UV-B-induced MMP-1 expression and JNK activation by NK-CdM suggests NK-CdM as a possible candidate anti-skin aging agent.

• Clinical and Experimental Reproductive Medicine
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• 제36권3호
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• pp.199-207
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• 2009

목 적: 말초혈액 자연살해세포가 증가된 반복유산 환자군과 증가되지 않은 반복유산 환자군에서 다음 번 유산 시탈락막의 자연살해세포의 발현양상을 관찰하여 말초혈액 자연살해세포와 상관관계가 있는지 보고자 하였다. 연구방법: 말초혈액 자연살해세포가 15% 이상 증가된 반복유산 환자군 14명을 실험군으로, 15% 이하인 군 12명을 대조군으로 하여 연구를 진행하였다. 이 환자들에게서 다음 번 유산 시 착상부위를 포함한 자궁 탈락막 세포를 확인하여 면역조직화학염색을 통해 $CD56^+$와 $CD16^+$ 자연살해세포의 수를 세어 실험군과 대조군을 비교하였다. 결 과: 실험군과 대조군은 탈락막 내 $CD56^+$ 자연살해세포의 수 간에 통계적으로 유의한 차이 ($170.1{\pm}132.1$ vs. $68.3{\pm}66.1$, p=0.02)를 보였으나 둘 간의 상관관계 (r=0.229, p=0.261)는 없었다. 또한 두 군간에 $CD16^+$ 자연살해세포는 통계적으로 유의한 차이 ($25.70{\pm}11.72$ vs. $31.17{\pm}22.67$)를 보이지 않았다. 결 론: 본 연구는 말초혈액 $CD56^+$ 자연살해세포가 증가된 반복유산 환자군에서 말초혈액 자연살해세포가 증가되지 않은 군에 비하여 탈락막의 $CD56^+$ 자연살해세포가 증가되어 있음을 알 수 있었다. 이는 탈락막 자연살해세포가 반복유산의 면역학적 기전에서 중요한 역할을 할 것이라는 가능성을 제시해 주는 연구 결과이며 또한 말초혈액 자연살해세포의 측정이 반복유산 환자에서 다음 번 유산을 예측할 수 있는 유용한 지표임을 알 수 있다.

• Clinical and Experimental Pediatrics
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• 제46권12호
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• pp.1266-1270
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• 2003

저자들은 비강내 종괴로 내원한 14세 환아에서 종괴 생검 및 면역 표현형 검사로 비강 T/NK 세포형 림프종으로 진단하고 치료 중인 1례를 보고하는 바이다.

• IMMUNE NETWORK
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• 제6권1호
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• pp.6-12
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• 2006

Background: The Hypothalamo-Pituitary-Adrenal (HPA) axis is an important regulator for the body's stress response. As a primary stress responsive system, HPA-axis secretes various neurotransmitters, hormones, and cytokines, which regulates the immune system. Natural killer (NK) cell which is plays an important role in the innate immune response, is specially decreased their numbers and loose cytolytic activity in response to stress. However, the effect of HPA-axis secreted proteins on NK cell activity has not been defined. Herein, we studied the effect of adrenal secreted adiponectin on NK cell cytotoxicity. Adiponectin which is well-known metabolic control protein, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. Methods: Signal sequence trap was used to find stress novel secretory protein from HP A-axis. Selected adiponectin was treated mouse mature primary NK cells and then examined the effect of adiponectin to NK cell cytotoxicity and cytokine expression level. Results: We found that adiponectin which is secreted from adrenal gland, suppress IL-2 induced NK cell cytotoxicity. And also investigated cytolytic cytokines are suppressed by adiponectin. Conclusion: These data suggest that adiponectin inhibites NK cell cytotoxicity via suppression of cytotoxicity related target gene.

• IMMUNE NETWORK
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• 제7권3호
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• pp.133-140
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• 2007

Background: It is well established that cross talk between natural killer (NK) cells and myeloid dendritic cells (DC) leads to NK cell activation and DC maturation. In the present study, we investigated whether type 1-polarized DC (DC1) matured in the presence of IFN-${\gamma}$ and type 2-polarized DC (DC2) matured in the presence of PGE2 can differentially activate NK cells. Methods: In order to generate DC, plastic adherent monocytes were cultured in RPMI 1640 containing GM-CSF and IL-4. At day 6, maturation was induced by culturing the cells for 2 days with cytokines or PGE2 in the presence or absence of LPS. Each population of DC was cocultured with NK cells for 24 h. The antigen expression on DC was analyzed by flow cytometry and cytokine production in culture supernatant was measured by ELISA or a bioassay for TNF-${\alpha}$ determination. NK cell-mediated lysis was determined using a standard 4h chromium release assay. Results: DC2, unlike DC1, had weak, if any, ability to induce NK cell activation as measured by IFN-${\gamma}$ production and cytolytic activity. DC2 were weakly stimulated by activated NK cells compared to DC1. In addition, IFN-${\gamma}$-primed mature DC appeared to be most resistant to active NK cell-mediated lysis even at a high NK cell/DC ratio. On the other hand, PGE2-primed DC were less resistant to feedback regulation by NK cells than IFN-${\gamma}$-primed mature DC. Finally, we showed that the differential effect of two types of DC population on NK cell activity is not due to differences in their ability to form conjugates with NK cells. Conclusion: These results suggest that different combinations of inflammatory mediators differentially affect the effector function of DC and, as a result, the function of NK cells, eventually leading to distinct levels of activation in adaptive immunity.

• 한양메디칼리뷰
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• 제33권1호
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• pp.59-64
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• 2013

Cancer remains the leading cause of death worldwide despite intense efforts in developing innovative treatments. Current approaches in cancer therapy are mainly directed to a selective targeting of cancer cells to avoid potential side effects associated with conventional therapy. In this respect, Natural killer (NK) cells have gained growing attention and are now being considered as promising therapeutic tools for cancer therapy owing to their intrinsic ability to rapidly recognize and kill cancer cells, while sparing normal healthy cells. NK cells play a key role in the first line of defense against transformed and virus-infected cells. NK cells sense their target through a whole array of receptors, both activating and inhibitory. Functional outcome of NK cell against target cells is determined by the balance of signals transmitted from diverse activating and inhibiting receptors. Despite significant progress made in the role of NK cells attack as a pivotal sentinel in tumor surveillance, the molecular has been that regulate NK cell responses remain unclear, which restricts the use of NK cells as a therapeutic measure. Accordingly, current efforts for NK cell-based cancer therapy have largely relied on the strategies that are based on the manipulation of inhibitory receptor function. However, if we better understand the mechanisms governing NK cell activation, including those mediated by diverse activating receptors, this knowledge can be applied to the development of optimal design for cancer immunotherapy by targeting NK cells.

• Journal of Acupuncture Research
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• 제19권2호
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• pp.221-230
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• 2002

Some studies report that electroacupuncture(EA) boost natural killer cell(NK cell) activity. And also it is well known that hypothalamus is deeply related to effects of EA on analgesia. Some reports said that especially lateral hypothalamic area(LHA) is related to splenic NK cell activity. In order to investigate the relation between hypothalamus and effects of EA at ST36 point on NK cell activity of Spraque-Dawley rats. Lesions were made bilaterally at lateral hypothalamic area(LHA). And NK cytotoxities of normal and lesioned rats were measured with 51Cr release immunoassay after EA stimulation for 2 and 14 days. NK cell activity of EA group was significantly higher than sham group at 2nd, 14th day in normal rats. And LHA lesions abolished effects of EA on NK cell activity at 2nd day. But LHA lesions did not affect the effects of EA at 14th days. We also had an evidence that the decrease of NK cell activity was almost recoverd at 14th day. These results strongly suggest that LHA is deeply related to increase of NK cell activity induced by EA.

• Oncology Letters
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• 제41권5호
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• pp.2625-2635
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• 2019

The majority of natural killer (NK) cells serve an important role in eliminating malignant cells. The cytotoxic effects of NK cells were first identified against leukemia cells, and it is now hypothesized that they may have a critical role in leukemia therapy. The cellular functions of NK cells are mediated by their cell surface receptors, which recognize ligands on cancer cells. The role of NK cells is specifically regulated by the activating or inhibitory killer cell immunoglobulin-like receptors (KIRs) on their surface, which bind to the human leukocyte antigen (HLA) class I ligands present on the target cells. The association between KIR and HLA is derived from the diversity of KIR/HLA gene profiles present in different individuals, and this determines the cytotoxic effect of NK cells on cancer cells. Chronic myeloid leukemia (CML) is a hematological leukemia characterized by the hyper-proliferation of myeloid cells, with the majority of patients with CML presenting with abnormal immune cells. Tyrosine kinase inhibitors are the present standard therapy for CML, but are associated with numerous adverse side effects. Various studies have proposed CML therapy by immunotherapeutic approaches targeting the immune cells. This review summarizes the contents of NK cells and the association between KIR/HLA and leukemia, especially CML. This is followed by a discussion on the development of NK cell immunotherapy in hematological malignancies and research into strategies to enhance NK cell function for CML treatment.