• Clinical and Experimental Reproductive Medicine
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• 제38권3호
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• pp.168-173
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• 2011

Objective: To examine the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and hyperhomocysteinemia in women with unexplained recurrent miscarriages (RM) and to investigate the association between MTHFR genotype variants and alloimmune activation, proportion of peripheral blood natural killer (pbNK) cells. Methods: A total of 39 patients with a history of two or more unexplained miscarriages were recruited to this study. The controls were women who had a live birth without a history of RM (n=50). The proportion of pbNK cells was measured by flow cytometry. Plasma homocysteine levels and the incidence of the MTHFR variant of the RM and control groups were compared. The proportion of pbNK cells was compared to the MTHFR variants in the RM group. Results: No differences were found between the two groups' mean plasma homocysteine levels ($7.6{\pm}1.5{\mu}mol$/L vs. $7.1{\pm}2.1{\mu}mol$/L) or incidence of the MTHFR genotype variant (CC, 35% vs. 33%; CT, 40% vs. 53%; and TT, 25% vs. 14%). In the RM group, individuals with the TT variant ($7.7{\pm}1.1{\mu}mol$/L) had higher homocysteine levels than those with the CC and CT variants ($7.4{\pm}1.9{\mu}mol$/L and $7.4{\pm}1.2{\mu}mol$/L) and those with the CT variant ($19.2{\pm}8.1%$) had a higher proportion of CD3-/CD56+ pbNK cells than those with the CC and TT variants ($17.7{\pm}6.6%$ and $17.9{\pm}7.0%$), but the results of both comparisons were statistically insignificant. Conclusion: These preliminary results show no difference in plasma homocysteine levels between the RM and control groups or among MTHFR genotype variants in the RM group, which may suggest that the plasma homocysteine level is difficult to use as a predictive marker of RM in the Korean population. A study of a larger number of patients is needed.

• Journal of Acupuncture Research
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• 제32권1호
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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.

• 생명과학회지
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• 제33권3호
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• pp.295-303
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• 2023

면역 체계와 대사 체계는 항상성을 유지하는데 중요한 요소이다. 면역 반응과 대사 조절은 연관성이 높아, 정상적인 대사가 교란되면 대사 질환이 발생하며, 면역 반응에도 변화가 발생하였다. 마찬가지로, 비만은 면역 반응과 높은 관련이 있다. 에너지 대사의 불균형으로 발생하는 비만은 인슐린 저항성, 제2형 당뇨병, 지방간 질환, 동맥경화증, 고혈압 등의 대사 질환과 관련이 있다. 알려진 바로는, 비만은 낮은 수준의 염증이 만성화된 상태가 특징이다. 비만 환경에서, 면역세포의 미세 환경은 대식세포, 자연살해세포, T세포 같은 면역세포의 독특한 활성화 표현형에 의해 염증성이 되었다. 또한, 면역 세포는 세포 간의 기전, 사이토카인을 매개하는 기전을 통해 상호작용하여 비만으로 인한 염증 반응을 강화한다. 이러한 현상은 기존의 췌장 리파아제나 알파-아밀라아제 같은 체내 효소의 억제나 지방전구세포의 분화를 억제를 표적으로 하는 일반적인 비만의 약리학적 치료 외에 면역세포 활성화 조절을 표적으로 하는 비만의 약리학적 치료 전략을 시사한다. 본 논문에서는 대식세포, 자연살해세포, T세포의 활성화 표현형과 비만 환경 내이들의 양상에 대해 정리하였다. 또한, 본 논문에서는 현재까지 확인된 면역세포의 활성화 조절을 통한 비만을 완화하는 약리학적 물질에 대해서 정리하였다.

• 대한한방소아과학회지
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• 제8권1호
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• pp.39-58
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• 1994

Even though appropriate immune response is necessary for the survival of the individual, excessive or insufficient immune response might cause autoimmune or allergic disease respectively. So the immune response must be controlled to the degree that is beneficial for the well being of the individual. This study was undertaken to know the effects of Junsibaekchulsan(JB) on the immune system od the mouse. For the evalulation of the cell-mediated immunity(CMI), delayed-type hypersensitivity against dinitrofluorobenzene(DNFB) were measured, and humoral immunity, hemagglutinin and hemolysin titers against SRBCs(sheep red blood cells) were measured, and rosette formation of spleen cells with SRBCs were measured. For the evaluation of innate immunity, phagocytic activity of macrophages, natural killer cell activity, and reactive nitrogen and oxygen intermediates were measured. The results are as follows: 1. The administration of JB depressed the antibody formation (hemagglutinin and hemolysin) against SRBCs. 2. The administration of JB did not affect the delayed-type hypersensitivity against DNFB. 3. The administration of JB did not affect the cytotoxic activity of natural killer cells. 4. The administration of JB increased the phagocytic activity of macrophages. 5. The administration of JB increased the rosette formating cells of the spleen cells. 6. The exposure of JB induced the secretion of reactive nitrogen intermediates but administration of JB deperssed the production of reactive oxygen intermediates. Administration of JB selectively depressed the humoral immune response without affecting CMI and innate immunity. These results of JB on the immune system might be useful for the treatment of such.

• Journal of Microbiology and Biotechnology
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• 제29권9호
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• pp.1444-1452
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• 2019

The conventional prophylactic vaccines for human papillomavirus (HPV) efficiently prevent infection with high-risk HPV types, but they do not promote therapeutic effects against cervical cancer. Previously, we developed HPV16 E7-expressing Lactobacillus casei (L. casei-E7) as a therapeutic vaccine candidate for cervical cancer, which induces antitumor therapeutic effects in a TC-1 murine cancer model. To improve the therapeutic effect of L. casei-E7, we performed co-treatment with poly-gamma-glutamic acid (${\gamma}-PGA$), a safe and edible biomaterial naturally secreted by Bacillus subtilis. We investigated their synergistic effect to improve antitumor efficacy in a murine cancer model. The treatment with ${\gamma}-PGA$ did not show in vitro cytotoxicity against TC-1 tumor cells; however, an enhanced innate immune response including activation of dendritic cells was observed. Mice co-administered with ${\gamma}-PGA$ and L. casei-E7 showed significantly suppressed growth of TC-1 tumor cells and an increased survival rate in TC-1 mouse models compared to those of mice vaccinated with L. casei-E7 alone. The administration of ${\gamma}-PGA$ markedly enhanced the activation of natural killer (NK) cells but did not increase the E7-specific cytolytic activity of $CD8^+$ T lymphocytes in mice vaccinated with L. casei-E7. Overall, our results suggest that oral administration of ${\gamma}-PGA$ induces a synergistic antitumor effect in combination with L. casei-E7.

• BMB Reports
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• 제54권1호
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• pp.44-58
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• 2021

Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers.

• 대한의생명과학회지
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• 제29권4호
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• pp.371-375
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• 2023

Natural killer (NK) cells are innate immune cells and play important roles as the first immune cells to recognize and kill cancer. In patients with advanced and terminal cancer, NK cells are often inactivated, suggesting that NK cells may play important roles in cancer treatment. In particular, the proportion of NK cells among immune cells infiltrating tumor tissues is often low, which suggests that NK cells do not survive in tumor microenvironment (TME). In order to overcome these hurdles of NK cells in cancer treatment, it is critical to develop strategies that enhance the proliferation and cytolytic activity of NK cells. We applied Vemurafenib to NK cells and measured the degree of NK cell proliferation and functional activation. We obtained unexpected results of increased NK cell numbers and anti-tumor activity after Vemurafenib treatment. Although further investigation is required to uncover the detailed mechanisms, our results suggest that Vemurafenib is a promising candidate to increase the efficacy of cancer immunotherapy using NK cells.

• Molecules and Cells
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• 제44권5호
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• pp.328-334
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• 2021

The advent of the major histocompatibility complex (MHC) multimer technology has led to a breakthrough in the quantification and analysis of antigen-specific T cells. In particular, this technology has dramatically advanced the measurement and analysis of CD8 T cells and is being applied more widely. In addition, the scope of application of MHC multimer technology is gradually expanding to other T cells such as CD4 T cells, natural killer T cells, and mucosal-associated invariant T cells. MHC multimer technology acts by complementing the T-cell receptor-MHC/peptide complex affinity, which is relatively low compared to antigen-antibody affinity, through a multivalent interaction. The application of MHC multimer technology has expanded to include various functions such as quantification and analysis of antigen-specific T cells, cell sorting, depletion, stimulation to replace antigen-presenting cells, and single-cell classification through DNA barcodes. This review aims to provide the latest knowledge of MHC multimer technology, which is constantly evolving, broaden understanding of this technology, and promote its widespread use.

• Molecules and Cells
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• 제25권2호
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• pp.178-183
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• 2008

To investigate the effects of electro-acupuncture (EA) treatment on regions remote from the application, we measured cellular, enzymatic, and transcriptional activities in various internal tissues of healthy rats. The EA was applied to the well-identified acupoint ST36 of the leg. After application, we measured the activity of natural killer cells in the spleen, gene expression in the hypothalamus, and the activities of antioxidative enzymes in the hypothalamus, liver and red blood cells. The EA treatment increased natural killer cell activity in the spleen by approximately 44%. It also induced genes related to pain, including 5-Hydroxytryptamine (serotonin) receptor 3a (Htr3a) and Endothelin receptor type B (Ednrb) in the hypothalamus, and increased the activity of superoxide dismutase in the hypothalamus, liver, and red blood cells. These findings indicate that EA mediates its effects through changes in cellular activity, gene expression, and enzymatic activity in multiple remote tissues. The sum of these alterations may explain the beneficial effects of EA.

• 한국산업보건학회지
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• 제26권3호
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• pp.286-292
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• 2016

Objectives: This study aimed to evaluate the effects of chronical exposure to high-level dusts on cellular immune function. Methods: The subjects were 110 male workers, among whom 60 were chronically exposed to high-level dusts in mica, limestone and iron mines. The remaining 50 were office workers. Ambient total, respirable dust and crystalline silica in the workplace were sampled using personal air samplers and analyzed according to NIOSH method 0500. Serum levels of hydrogen peroxide, lipid peroxide and superoxide misutase activity were measured using absorption chromatography. The subpopulations of CD4+, CD8+, natural killer cells (CD16+) and CD3+ T-lymphocytes were examined by two-color staining using monoclonal antibodies. Results: The concentration of hydrogen peroxide was significantly higher in exposed workers and superoxide dismutase activity was significantly higher in control workers. No significant difference in numbers of T-lymphocyte subpopulations were observed between exposed and control workers. A significant correlation in exposed workers was observed among total dusts, respirable dusts and crystalline silica. Hydrogen peroxide was significantly correlated with total dust (r=0.720, p<0.01), respirable dust (r=0.770, p<0.01) and crystalline silica (r=0.678, p<0.01). Concentration of hydrogen peroxide showed a significantly negative correlation with numbers of CD8+ cells (r=-0.274, p<0.01), CD3+ cells (r=-0.222, p<0.01) and natural killer cells (r=-0.556, p<0.01). Conclusions: These results suggest that chronical exposure to high-level dust affects cellular immune function and effects might mediate through reactive oxygen species and inflammatory response.