• Title/Summary/Keyword: Natural Killer cell

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The Emerging Role of Natural Killer Cells in Innate and Adaptive Immunity

  • Kim, Eun-Mi;Ko, Chang-Bo;Myung, Pyung-Keun;Cho, Daeho;Choi, Inpyo;Kang, Hyung-Sik
    • IMMUNE NETWORK
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    • v.4 no.4
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    • pp.205-215
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    • 2004
  • In the early host defense system, effector function of natural killer (NK) cells results in natural killing against target cells such as microbe-infected, malignant, and certain allogenic cells without prior stimulation. NK cell cytotoxicity is selectively regulated by homeostatic prevalence between a repertoire of both activating and inhibitory receptors, and the discrimination of untransformed cells is achieved by recognition of major histocompatibility complex (MHC) class I alleles through inhibitory signals. Although it is well known that the bipotential T/NK progenitors are derived from the common precusor, functional mechanisms in terms of the development of NK cells remain to be further investigated. NK cells are mainly involved in innate immunity, but recent studies have been reported that they also play a critical role in adaptive immune responses through interaction with dendritic cells (DC). This interaction will provide effector functions and development of NK cells, and elucidation of its precise mechanism may lead to therapeutic strategies for effective treatment of several immune diseases.

Natural killer cell activity in Naegzeria fowleri infected mice (Naegleria fowleri 자연살세포의 활성에 미치는 영향)

  • Lee, Gyu-Rae;Sin, Ju-Ok;Im, Gyeong-Il
    • Parasites, Hosts and Diseases
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    • v.29 no.3
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    • pp.267-278
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    • 1991
  • The natural killer (NK) cell activity of splenocytes and recycling capacity of NK cells were observed by combining the $^{51}Cr-release$ cytotoxicity assay and single cell cytotoxicity assay against YAC-1. The ICR mice were infected intranasally with Naegleria fewleri, that is a pathogenic free-living amoeba. The mice infected with $1{\times}10^5$ trophosoites showed mortality rate of 76.7% and mean survival time of 12. 9 days. The cytotoxic activity of NK cells in infected mice was significantly higher than that of non-infected mice during the period between 12 hours and day 3 after infection, and highest on day 1. The target-binding capacity of NK cells in infected mice was not different from that of non-infected ones. Maximal killing potential and maximal recycling capacity were remarkably increased in infected mice as compared with the control. The results obtained in this observation indicated that elevated NK cell activity in mice infected with N. fowieri was not due to target-binding capacity of NK cells but due to the increased activity of NK cells and increased recycling capacity of individual NK cells.

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Upregulation of Myc promotes the evasion of NK cell-mediated immunity through suppression of NKG2D ligands in K562 cells

  • Young-Shin Lee;Woong Heo;Cheol-Hun Son;Chi-Dug Kang;You-Soo Park;Jaeho Bae
    • 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.

Ki-67 Can Predict the Response to the Gemcitabine, Oxaliplatin And L-asparaginase Regimen (GELOX) and Prognosis in Patients with Nasal Natural Killer/T-cell Lymphoma

  • Zhang, Jing;Jiang, Wei;Wang, Wei-Da;Liu, Cheng-Cheng;Hu, Yan-Ping;Xia, Zhong-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4515-4520
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    • 2015
  • GELOX (gemcitabine, oxaliplatin and L-asparaginase) regimen showed an impressive result in our previous study, but the effect of this new regimen is still dissatisfying for some patients, so it is necessary to identify which patients will benefit from this regimen. A total of fifty-one cases with nasal natural killer/T-cell lymphoma receiving initial GELOX chemotherapy were enrolled in this study. The ki-67 expression detected by immunohistochemistry (IHC) in the specimens ranged from 10% to 90%, with a median value of 70%, so cases higher than the median value (${\geq}70%$) were defined as high ki-67 expression, and the others were designated as low ki-67 expression. The response rate had no statistical difference between low ki-67 expression group and high ki-67 expression group (P=0.291) though the value in the former group was relatively high. After a median follow-up of 18.03 months, the 3-year progression-free survival (PFS) for patients with low ki-67 expression was significantly higher than those with high ki-67 expression (83.8% vs. 47.9%, P=0.038). In the stage I/II subgroup, 3-year PFS and overall survival (OS) were statistically higher in the patients with low ki-67 expression than those with high ki-67 expression. Multivariate analysis revealed high ki-67 expression was an independent prognostic factor for PFS. These results suggest that low ki-67 expression can predict a good response of GELOX in these patients, and the combination of ki-67 expression and early stage is helpful to identify an excellent prognosis subgroup from patients receiving GELOX in this disease.

3 Cases of Cancer Patients Whose Natural Killer Cell Activity Improved with Traditional Korean Medicine Treatment: A Case Series (한방치료 후 NK세포 활성도의 호전을 보인 암환자 증례보고 3례)

  • Park, Chan-ran;Kim, Eun-ji;Son, Chang-gue;Cho, Jung-hyo;Lee, Nam-hun
    • The Journal of Internal Korean Medicine
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    • v.42 no.3
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    • pp.444-454
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    • 2021
  • Objectives: High natural killer cell activity (NKA) is associated with a clinically favorable status in patients with cancer. This study explores whether traditional Korean medicine (TKM) improves NKA in patients with cancer. Methods: We report three clinical cases involving patients with cancer who underwent NKA tests while they received TKM treatment, including acupuncture, moxibustion, wild ginseng pharmacopuncture, and Korean herbal medicines. We analyzed the treatment process and NKA test results of each patient. Results: The NKA of all three patients presented with an increasing tendency during the treatment process. Patient 1, who had been diagnosed with breast cancer, received inpatient treatment 3 times between September 16, 2017 and February 27, 2019. The NKA increased from 7.2 pg/mL to 571.7 pg/mL. Patient 2, who had thyroid cancer, was hospitalized 4 times between July 23, 2019 and August 27, 2020. The NKA improved from 317.4 pg/mL to 2000 pg/mL. Patient 3, who had liver cancer, received inpatient treatment 4 times between May 27, 2016 and January 10, 2017. The NKA increased from 22.2 pg/mL to 459.5 pg/mL. The chief complaints of these patients also were alleviated. Conclusions: TKM may be an effective treatment for accelerating NKA. Further research is needed to establish evidence that TKM stimulates NKA.

Development of a Platform for Natural Killer Cell Therapy with Antiviral Efficacy (항바이러스 효능을 가진 자연살해세포 치료제 플랫폼 개발)

  • Dongsoo Kim;Hyeongseok Yun;Jinhui Lee;Dayoung Yeon;Chi Ho Yu;Se Hum Gu;Young-Jo Song;Jung-Eun Kim;Seung-Ho Lee;Yong Han Lee;Gyeung Haeng Hur;Junghwa Kang
    • Journal of the Korea Institute of Military Science and Technology
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    • v.27 no.1
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    • pp.107-115
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    • 2024
  • Various vaccines were rapidly developed during the COVID-19 pandemic to prevent and treat infections but global infections continue, and concerns about new mutations and infectious diseases persist. Thus, active research focuses on developing, producing, and supplying vaccines and treatments for various infectious diseases and potential pandemics. Natural killer(NK) cells, as innate immune cells, can recognize and eliminate abnormal cells like virus-infected and cancer cells. Hence, their development as anticancer and antiviral treatments is rapidly advancing. In this study, optimal short-term culture conditions were identified for allogeneic NK cells by simplifying the culture process through the isolation of NK cells(referred to as NKi cells) and eliminating CD3+ cells(referred to as CD3- cells). NK cells demonstrated reduced viral titer in injection of NK cells into SARS-CoV-2 infected ACE-tg mice increased survival. The study's findings could form the basis for an antiviral treatment platform that swiftly responds to new viral disease pandemics.

Snake Venom-enhanced Cytotoxic Effect of Natural Killer Cells on A549 Human Lung Cancer Cell Growth (사독의 인체 폐암세포(A549)에 대한 Natural Killer 세포 세포독성 촉진 효과)

  • Lee, Ji In;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.32 no.1
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    • pp.79-88
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    • 2015
  • Objectives : The purpose of this research was to investigate the cytotoxic effect of Natural Killer(NK)-92 cell and Snake Venom, and to elucidate its mechanism on human lung carcinoma cell A549. Methods : In order to figure out whether Snake Venom enhances the cytotoxic effect of NK-92 cell in A549 cell, Cell Viability Assay was conducted. Also, in order to observe the changes of Caspase-3 and Caspase-8, both of which are proteinases that advance apoptosis, and the changes of TNRF and DR3, which are Death Receptors of the extrinsic pathway of apoptosis, Western Blot Analysis was conducted. By conducting RT-PCR analysis, we have tried to confirm Perforin, Granzyme B, and GADPH, all of which are cytotoxic-related proteins. Lastly, in order to observe the effect of Snake Venom on NO formation within human lung carcinoma cells, NO determination was conducted. Results : 1. After conducting Cell Viability Assay, Snake Venom enhanced the cytotoxic effect of NK-92 cell and inhibited the growth of A549. 2. Western Blot Analysis caused proteinases Caspase-3 and Caspase-8, which advance apoptosis, to increase in the combined treatment group, but not in treatment groups that focused only on either Snake Venom or NK-92 cell in A549 lung carcinoma cells. 3. Western Blot Analysis caused an expression of TNFR2 and DR3, both of which are Death Receptors of the apoptosis extrinsic pathway, in the combined treatment group, but not intreatment groups that focused only on either Snake Venom or NK-92 cell in A549 human lung carcinoma cells. 4. After conducting NO determination, NO formation within A549 cell showed no significant changes in both treatment groups that focused NK-92 cell and combined treatment group. 5. After conducting RT-PCR, the expression of Granzyme B and Perforin, which are cytotoxic-related proteins within A549 human lung carcinoma cells, showed growth in the combined treatment group, but not the treatment group that focused only on NK-92 cell. Conclusion : It has been indicated that, when it comes to the A549 cell, Snake Venom enhances the increase of Death Receptor expression and continuous apoptosis reaction, leading to the enhancement of the cancer cell cytotoxic effect of the NK-92 cell. It is expected that Snake Venom can be used with the NK-92 cell for further lung cancer treatment.

Body Fat Percentage and Natural Killer Cell Activity of Breast and Rectal Cancer Patients after Diagnosis but before Treatment (진단 직후 유방암.직장암 환자의 체지방량과 자연 살 세포 활동량)

  • Kim, Dal-Sook;Jun, Myung-Hee
    • Journal of Korean Academy of Nursing
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    • v.38 no.2
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    • pp.321-331
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    • 2008
  • Purpose: To examine the relationship between body fat percentage (BFP) and N-K cell activity (NKCA) in Korean breast and rectal cancer patients just after diagnosis. Methods: With 35 subjects enrolled between November 2002 and May 2003, Bioelectrical Impedance Analysis was used to estimate BFP. FACS Analysis was used to measure N-K cell activity. The relationships between BFP and NKCA were identified by using curve estimation, simple regression, and multiple regression, Results: The mean BFPs of the subjects and all the sub-groups were higher than acceptable BFPs. Both the mean NKCAs of male and female subjects were lower than that of healthy women. NKCA was explained by BFP with a 14.9% variance in the total subjects (p<.05). There were significant negative relationships between BFP and NKCA after controlling age, type of cancer, and stage of cancer while no significant relationship was found after controlling for gender. The relationships between BFP and NKCA in the sub-groups of female, breast cancer, and stage I, and II were significant. The relationships between male, rectal cancer, and the stage III, and VI sub-groups were not identified, but they revealed a mild to moderate steep in curve estimation. Conclusion: Weight reduction could prevent the risk and advancement of breast and rectal cancer in Koreans.

Effects of Daturae Flos and Daturae Semen Extract on the Immunocyte Response in Mice (만타라화(曼陀羅花) 및 만타라자(曼陀羅子) 수추출물(水抽出物)이 마우스의 면역세포기능(免疫細胞機能)에 미치는 영향(影響))

  • Ko, Woon-Che;Song, Ho-Joon;Shin, Min-Kyo
    • Korean Journal of Pharmacognosy
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    • v.21 no.4
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    • pp.307-316
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    • 1990
  • This study was undertaken to test the effects of Daturae Flos(DF) and Daturae Semen(DS) on the cellular and humoral immune responses, and the functions of the cells involved in immunoinflammation. Both extracts decreased the activity of superoxide dismutase, and the decrease was greater in the mouse group which was treated with DS. Both extracts decreased the phagocytic activity as measured by assessing the number of the latex particle within the phagocyte after incubation of peritoneal macrophages with fluorochrome-labelled latex particle and decreased natural killer cell activity as measured by enumerating the viable YAC-1 cells after treatment of target cells with splenic natural killer cells. Both extracts also decreased the cell-mediated immunity in vivo as assessed by measuring the ear thickness after sensitization and challenge with dinitrofluorobenzene, however, had no effects on the humoral immune responses as measured by checking hemolysin and hemagglutinin titers after immunization with sheep red blood cells(SRBC). Extracts of Semen caused decrease in the number of rosette forming cells between the splenic cells and SRBC. The results of this study suggested that both Daturae extracts could depress the immunoinflammation by affecting the various cell types involved in inflammation.

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