• Journal of Microbiology and Biotechnology
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• v.32 no.5
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• pp.612-620
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• 2022

Recent studies have revealed that probiotics and their metabolites are present under various conditions; however, the role of probiotic metabolites (i.e., postbiotics in pathological states) is controversial. Natural killer (NK) cells play a key role in innate and adaptive immunity. In this study, we examined NK cell activation influenced by a postbiotics mixture in response to gut microbiome modulation in stress-induced mice. In vivo activation of NK cells increased in the postbiotics mixture treatment group in accordance with Th1/Th2 expression level. Meanwhile, the Red Ginseng treatment group, a reference group, showed very little expression of NK cell activation. Moreover, the postbiotics mixture treatment group in particular changed the gut microbiome composition. Although the exact role of the postbiotics mixture in regulating the immune system of stress-induced mice remains unclear, the postbiotics mixture-induced NK cell activation might have affected gut microbiome modulation.

• Preventive Nutrition and Food Science
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• v.3 no.3
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• pp.282-286
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• 1998

To determine the immune effect of kimchi extracts in mice, 0.5mg/day of the extracts from kimchis, which were prepared with conventionally (general kimchi)and organically(organic kimchi) cultivated ingredients, were treated orally to male BALB/c mice. Following 1, 3 and 5 weeks of treatment , the Interleukin-2(IL-2) production in the presence (con-A-stimulated )or the absence(spontaneous)of con A 95 $\mu\textrm{g}$/ml) and the natural killer cell (NK) activity of the splenocytes were measured. The IL-2 production in most of treatments with methanol extract from general kimchi were significantly higher than those of control(p<0.05).And at the 3 weeks of treatment, the spontaneous or con A-stimulated IL-2 productions from splenocytes of mice treated with it increased more than those of control group, by 2.8 and 2.2 times, respectively. However, the longer the treatment with methanol extracts from organic kimchi showed the higher the enhancing effect on the IL-2 production. The spontaneous or con A-stimulatdIL-2 productions form splenocytes of mice treated with dicholoromethyane fraction from general kimchi also increased at 5 weeks of treatment compared to those of control group, by 2.7 and 2.5 times, respectively. The natural killer cell activity of splenocytes from mice treated with methano lextracts from general kimchi for 1 ~5 weeks significantly higher than that of control goup (p<0.01). The effect of methano extracts from general kimchi was the highest at 3 weeks of treatment, as same as in the IL-2 production. The enhancing effect of methano extracts from organic kimchi on the NK cell activity was the highest at 5 weeks of treatment . The NK cell activity of splenocytes from mice treated with dichloromethane fraction from general kimchi for 5 weeks was significantly higher than those in control and 3 weeks of treatment. These results showed that the effects of kimchi extracts on the IL-2 production and the NK cell activity in mice were profound in long term of treatment (3 and 5 weeks than 1 week) . We suggest that kimchi extracts might have an immune effect in part due to its enhancing action on the IL-2 production and the NK cell activity.

• Journal of Ginseng Research
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• v.33 no.2
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• pp.99-103
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• 2009

The in-vitro immunomodulatory function of murine natural-killer (NK) cells induced by red-ginseng acidic polysaccharide (RGAP) in ovariectomized (OVX) rats was examined in this study. The IL-2-induced NK cell activity was significantly decreased in the OVX rats compared to the sham groups, but the normally induced NK cell activity was not. RGAP, however, increased the NK cell activity in both groups, and this effect involved iNOS expression. The inhibition of iNOS activity did not increase the NK cell cytotoxicity by RGAP in the OVX rats. The data that were obtained also demonstrated that the expression of iNOS was increased in the spleen of the OVX rats. These results indicate that RGAP increases the tumoricidal activity of the NK cell in the OVX rats, which is a primed or activated state of innate immune cells resulting from the changes in cytokine production induced by estrogen-deficient stress. Therefore, RGAP has a synergistic effect on the NK cell activities, which are regulated by the iNOS signals in OVX rats. This suggests that RGAP is useful for potential therapeutic strategies as a nutrient in regulating the NK cells in OVX rats.

• Journal of Microbiology and Biotechnology
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• v.33 no.7
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• pp.864-874
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• 2023

Natural killer (NK) cell dysfunctions against hepatocellular carcinoma (HCC) in a hypoxic environment. Many solid tumors are present in a hypoxic condition, which changes the effector function of various immune cells. The transcription of hypoxic-inducible factors (HIFs) in cancer cells make it possible to adapt to their hypoxic environment and to escape the immune surveillance of NK cells. Recently, the correlation between the transcription of HIF-1α and pro-inflammatory cytokines has been reported. Interleukin (IL)-6 is higher in cancers with a highly invasive ability, and is closely related to the metastasis of cancers. This study showed that the expression of HIF-1α in HCC cells was associated with the presence of IL-6 in the environment of HCC-NK cells. Blocking of IL-6 by antibody in the HCC-NK interaction changed the production of several cytokines including TGF-β, IL-1, IL-18 and IL-21. Interestingly, in a co-culture of HIF-1α-expressed HCC cells and NK cells, blocking of IL-6 increased the production of IL-21 in their supernatants. In addition, the absence of IL-6 significantly enhanced the cytotoxic ability and the expression of the activating receptors (NKG2D, NKp44, and NKG2C) in NK cells to HIF-1α-expressed HCC cells. These effects might be made by the decreased expression of HIF-1α in HCC cells through the inhibited phosphorylation of STAT3. In conclusion, the absence of IL-6 in the interaction of HIF-1α-expressed HCC cells and NK cells could enhance the antitumor activity of NK cells to HCC cells.

• Toxicological Research
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• v.14 no.4
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• pp.475-481
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• 1998

This study was performed to investigate the modifying effect of the general (GPA) and the fermented pilose antler (FPA) on experimental hepatocarcinogenesis and Natural Killer cell activity in rats. Specific pathogen free, 5-week male Sprague-Dawley rats were divided into four groups. To induce hepatocarcinogenesis, diethylnitrosamine (DEN, 200 mg/kg, i.p.) was used as a tumor initiator and was given in a single dose at experimental onset. All rats were given a partial hepatectomy (PH) at 3 weeks after experimental onset. Sodium phenobarbital (PB, 0.05% in diet), GPA (0.075% in diet) and FPA (0. 075% in diet) were given from 2 to 8 weeks. Group I of the initiation control group was only given DEN. As initiation-promotion group, Group II was given DEN and then PB. Group III and IV were given DEN-PB-GPA and DEN-PB-FPA, respectively. In hematological analysis, as compared with Group I. the number of white blood cells were significantly increased in the GPA (p<0.01) and the FPA treated group (p<0.05), respectively. Natural killer (NK) cell activity by flow cytometer (FCM) analysis was higher in group of treated with the GPA (35%) than that of the FPA (27.5%), but not significant. Result of the immunohistochemical staining of the glutathione S-transferase placental form (GST-p) indicated that the number of and area of the pre-neoplastic lesions was not significantly changed in Group III and IV compared Group II, respectively. In conclusion, the GPA and the FPA treatment significantly increased the number od WBC in peripheral blood, but the enhancing NK activity and the modifying effect on the experimental hepatocarcinogenesis were not observed.

• IMMUNE NETWORK
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• v.23 no.3
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• pp.22.1-22.15
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• 2023

Alcoholic liver cirrhosis (ALC) is caused by chronic alcohol overconsumption and might be linked to dysregulated immune responses in the gut-liver axis. However, there is a lack of comprehensive research on levels and functions of innate lymphocytes including mucosal-associated invariant T (MAIT) cells, NKT cells, and NK (NK) cells in ALC patients. Thus, the aim of this study was to examine the levels and function of these cells, evaluate their clinical relevance, and explore their immunologic roles in the pathogenesis of ALC. Peripheral blood samples from ALC patients (n = 31) and healthy controls (HCs, n = 31) were collected. MAIT cells, NKT cells, NK cells, cytokines, CD69, PD-1, and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. Percentages and numbers of circulating MAIT cells, NKT cells, and NK cells were significantly reduced in ALC patients than in HCs. MAIT cell exhibited increased production of IL-17 and expression levels of CD69, PD-1, and LAG-3. NKT cells displayed decreased production of IFN-γ and IL-4. NK cells showed elevated CD69 expression. Absolute MAIT cell levels were positively correlated with lymphocyte count but negatively correlated with C-reactive protein. In addition, NKT cell levels were negatively correlated with hemoglobin levels. Furthermore, log-transformed absolute MAIT cell levels were negatively correlated with the Age, Bilirubin, INR, and Creatinine score. This study demonstrates that circulating MAIT cells, NKT cells, and NK cells are numerically deficient in ALC patients, and the degree of cytokine production and activation status also changed. Besides, some of their deficiencies are related to several clinical parameters. These findings provide important information about immune responses of ALC patients.

• Archives of Pharmacal Research
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• v.22 no.3
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• pp.255-261
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• 1999

The effect of biphenyl dimethyl dicarboxylate (PMC) on the cellular and nonspecific immunosuppressions by ketoconazole (KCZ) was investigated in ICR mice. PMC at a dose of 6 mg/kg was administered orally to mice daily for 14 consecutive days. KCZ was suspended in RPMI 1640 medium and orally administered at 160 mg/kg/day 2 hrs after the administration of PMC. Immune responses of the delayed-type hypersensitively (DTH) reaction to sheep red blood cells (SRBC), phagocytic activity and natural killer (NK) cell activity were evaluated. DTH reaction to SRBC was enhanced to normal level by the combination of PMC and KCZ, as compared with treatment of KCZ alone. In the combination of PMC and KCZ, as compared with treatment of KCZ alone, there were also significant increases in activities of natural killer (NK) cells and phagocytes along with circulating leukocytes. These findings indicate that PMC shows a significant restoration from the immunotoixc status induced by KCZ.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.2
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• pp.119-129
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• 2008

Objective: The purpose of this study was to quantify decidual $CD56^+$ and $CD16^+$ NK cell subtype population and to evaluate the correlation between decidual NK cell expression and peripheral $CD56^+$ NK cell expression in women with a history of recurrent abortion and increased peripheral NK cells. Methods: Twenty-nine women with recurrent abortion and elevated peripheral $CD56^+$ NK cell percentage who had chromosomally normal conceptus were included in this study. Thirty-two women with recurrent abortion who had chromosomally abnormal conceptus were used as controls. Distribution of $CD56^+$ and $CD16^+$ NK cells in decidual tissues including implantation sites was examined by immunohistochemical staining. The degree of immunohistochemical staining was interpreted by score and percentage. Results: There was a significant difference in decidual $CD56^+$ NK cell score ($43.6{\pm}24.5$ vs. $23.9{\pm}16.3$ P =0.001) and $CD56^+$ NK cell percentage ($42.1{\pm}11.7$ vs. $33.9{\pm}15.8$ P =0.027) between increased peripheral NK cell group and control group. However, there was no statistically significant difference in decidual $CD16^+$ NK cell score ($18.7{\pm}9.5$ vs. $13.2{\pm}39.4$ P =0.108) and $CD16^+$ NK cell percentage ($24.7{\pm}5.9$ vs. $23.4{\pm}11.7$ P =0.599). There was no significant correlation between decidual NK cell score and peripheral NK cell percentage in increase peripheral NK cell group (peripheral $CD56^+$ NK cell percentage vs. decidual $CD56^+$ NK cell score, r=-0.016, P =0.932, peripheral $CD16^+$ NK cell percentage vs. decidual $CD16^+$ NK cell score, r=0.008, P =0.968). Conclusion: This study shows that $CD56^+$ decidual NK cells are increased in decidua of women exhibiting a history of recurrent abortion with increased $CD56^+$ peripheral NK cell. There was no significant correlation between decidual and peripheral NK cell increment in increase peripheral NK cell group. This study suggests the possibility that decidual NK cells may play an important role in the immune mechanism of recurrent abortion.

• Journal of Pharmacopuncture
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• v.17 no.1
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• pp.20-26
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• 2014

Objectives: The study aimed to determine changes in laboratory data for cancer patients receiving Korean medicine (KM) care, with a focus on patients' functional status, cancer-coagulation factors and cancer immunity. Methods: We conducted an observational study of various cancer patients in all stages admitted to the East-West Cancer Center (EWCC), Dunsan Korean Hospital of Daejeon University, from Mar. 2011 to Aug. 2011. All patients were under the center's multi-modality Korean-medicine-based inpatient cancer care program. The hospitalization stay at EWCC ranged from 9 to 34 days. A total of 80 patients were followed in their routine hematologic laboratory screenings performed before and after hospitalization. Patients were divided into three groups depending on the status of their treatment: prevention of recurrence and metastasis group, KM treatment only group, and combination of conventional and KM treatment group. The lab reports included natural killer cell count (CD16 + CD56), fibrinogen, white blood cell (WBC), lymphocytes, monocytes, neutrophil, red blood cell (RBC), hemoglobin, platelet, Erythrocyte Sedimentation Rate (ESR), and Eastern Cooperative Oncology Group (ECOG) performance status. Results: With a Focus on patients' functional status, cancer-coagulation factors and cancer immunity, emphasis was placed on the NK cell count, fibrinogen count, and ECOG scores. Data generally revealed decreased fibrinogen count, fluctuating NK cell count and decreased ECOG, meaning improved performance status in all groups. The KM treatment only group showed the largest decrease in mean fibrinogen count and the largest increase in mean NK cell count. However, the group's ECOG score showed the smallest decrease, which may be due to the concentration of late-cancer-stage patients in that particular group. Conclusions: Multi-modality KM inpatient care may have positive effect on lowering the cancer coagulation factor fibrinogen, but its correlation with the change in the NK cell count is not clear.

• Archives of Pharmacal Research
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• v.15 no.1
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• pp.20-29
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• 1992

Effects of squalene on cellular and non-specific immune responses and antitumor activity in mice were investigated. Cellular and non-specific immunological assay parameters adopted in the present study were delayed-type hypersensitivity reaction and resette forming cells (RFC) for cellular immunity, activities of natural killer (NK) cells and phagocyte for non-specific immunity. Squalene resulted in marked increases of cellular and non-specific immune functions and enhancement of host resistance to tumor challenge in dose-dependent manner.