• Korean Journal of Poultry Science
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• v.49 no.2
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• pp.69-77
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• 2022

Antimicrobial peptides (AMPs) play an important role in innate immunity against pathogenic infections. AMPs exterminate pathogenic bacteria by disrupting cell membranes or inhibiting intracellular molecules. NK-2, first identified in pigs and derived from NK-lysin, has antimicrobial effects against bacteria and parasites. In this study, chimeric peptides (cpNK) of chicken and pig NK-2 and cpNK-derived peptides (cpNK-a1 and cpNK-a2) were synthesized, and their antimicrobial effects against various pathogenic bacteria such as Escherichia coli, Salmonella spp., Listeria monocytogenes, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA) were investigated. The structure of chimeric peptides from chicken and pig NK-2, cpNK, include α-helix like NK-2 and peptide net charge was +9 like porcine NK-2. The cpNK peptide showed powerful bactericidal effects against most bacterial species, including MRSA, especially against gram-negative bacteria. Furthermore, cpNK-derived short peptides, cpNK-a1 and a2 also showed bactericidal activity, but the effects were weaker than those of cpNK. Therefore, we conclude that cpNK- and cpNK-derived short peptides have the potential to be used as antibiotic alternatives.

• Molecules and Cells
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• v.24 no.1
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• pp.1-8
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• 2007

Natural killer (NK) cells play a crucial role in innate immune system and tumor surveillance. NK cells are derived from $CD34^+$hematopoietic stem cells and undergo differentiation via precursor NK cells in bone marrow (BM) through sequential acquisition of functional surface receptors. During differentiation of NK cells, many factors are involved including cytokines, membrane factors and transcription factors as well as microenvironment of BM. NK cells express their own repertoire of receptors including activating and inhibitory receptors that bind to major histocompatibility complex (MHC) class I or class I-related molecules. The balance between activating and inhibitory receptors determines the function of NK cells to kill targets. Binding of NK cell inhibitory receptors to their MHC class I-ligand renders the target cells to be protected from NK cell-mediated cytotoxicity. Thus, NK cells are able to discriminate self from non-self through MHC class I-binding inhibitory receptor. Using intrinsic properties of NK cells, NK cells are emerging to apply as therapeutic agents against many types of cancers. Recently, NK cell alloactivity has also been exploited in killer cell immunoglobulin-like receptor mismatched haploidentical stem cell transplantation to reduce the rate of relapse and graft versus host disease. In this review, we discuss the basic mechanisms of NK cell differentiation, diversity of NK cell receptors, and clinical applications of NK cells for anti-cancer immunotherapy.

• Biomedical Science Letters
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• v.29 no.4
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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.

• Journal of Microbiology and Biotechnology
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• v.30 no.8
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• pp.1222-1226
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• 2020

Lactobacillus reuteri NK33 (NK33) and Bifidobacterium adolescentis NK98 (NK98) alleviate immobilization stress-induced depression. To understand the gut microbiota-mediated mechanisms of NK33 and NK98 against depression, we examined their effects on Escherichia coli K1 (K1)-induced depression and gut dysbiosis in mice. NK33, NK98, and their mixtures (1:1, 4:1, and 9:1) mitigated K1-induced depression and colitis. NK33 and NK98 additively or synergistically increased BDNF⁺/NeuN⁺ cell population and suppressed NF-κB action in the hippocampus. They alleviated gut dysbiosis by reducing the Proteobacteria population and increasing the Clostridia population. These results suggest that NK33 and NK98 may alleviate depression and colitis by ameliorating gut dysbiosis.

• IMMUNE NETWORK
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• v.5 no.4
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• pp.247-251
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• 2005

Background: Natural killer (NK) cells are CD3 (-) CD14 (-) CD56 (+) lymphocytes. They play an important role in the body's innate immune response. They can induce spontaneous killing of cancer cells or virus-infected cells via the Fas/Fas ligand or the granzyme/perforin systems. The corticotropin-releasing hormone (CRH) is an important regulator for the body's stress response. It promotes proliferation and migration of various cancer cells through the CRH type 1 receptor under stress, and also inhibits NK or T cell activity. However, the relationship of CRH and NK cell migration to the target has not been confirmed. Herein, we study the effect of CRH on NK cell migration. Methods: We used the human NK cell line, NK-92MI, and tested the expression of CRH receptor type 1 on NK-92MI by RT-PCR. This was to examine the effect of CRH on tumor and NK cell migration, thus NK cells (NK-92MI) were incubated with or without CRH and then each CRH treated cell's migration ability compared to that of the CRH untreated group. Results: We confirmed that CRH receptor type 1 is expressed in NK-92MI. CRH can decrease NK cell migration in a time-/dose-dependent manner. Conclusion: These data suggest CRH can inhibit NK cell migration to target cells.

• Korean Journal of Organic Agriculture
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• v.19 no.4
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• pp.553-563
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• 2011

This experiment was conducted to determine the effect of nattokinase (NK) additives on milk production and composition, and blood metabolites in dairy cows. The two kinds of nattokinase with high fibrinolytic activity were produced by two strains of bacteria, Bacillus amyloliquefacines (NK1) and Bacillus subtilis (NK2). Total fifteen Holstein cows (average $1.83{\pm}0.37$ parity; average milk yield $23.2{\pm}3.2$ kg/d) were randomly assigned to three treatments (5 animals per treatment). Cows were fed TMR supplemented with 0g, 100g and 100g for control, NK1 and NK2 treatment, respectively for 4 weeks. Milk yield was significantly higher (p<0.05) for NK1 (22.89 kg/d) than for control (21.07 kg/d) and NK2 (21.36 kg/d). Somatic cell counts in NK treatments were significantly lower than that in control group (58,000 vs. 21,000 and 35,000 cells/ml, control vs. NK1 and NK2). Serum ALT levels in all treatment were similar to the range of 32.00~35.83 IU/L, but AST levels in NK1 (85.67 IU/L) was significantly decreased compared with those in control and NK2 (121.67 and 117.67 IU/L respectively). Serum T-CHO levels in NK1 (145.33 mg/dl) was significantly decreased (p<0.05) compared with that in control (179.00 mg/dl) and NK2 (176.17 mg/dl). This finding showed that NK1 additives could possibly have a positive effect in lactation performance of mid-lactation dairy cows by increasing milk yield, reducing somatic cell count, improving liver function and decreasing cholesterol in blood.

• Biomedical Science Letters
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• v.29 no.4
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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.

• Journal of Microbiology and Biotechnology
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• v.32 no.4
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• pp.397-404
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• 2022

Natural killer (NK) cell activity is more attenuated in hepatocellular carcinoma (HCC) patients than normal. Hypoxic-inducible factor (HIF)-1α is highly expressed in tumors to maintain their metabolism in a hypoxic environment. The expression of HIF-1α in cancers can lead to cell growth, proliferation, invasion/metastasis and immune escape. Although apigenin, a flavonoid, is known to have various biological activities, it has not been demonstrated in NK cell immune activity in HCC cells. In this study, NK-92 cells were directly cocultured with HCC SK-Hep1 cells for 24 h to evaluate NK cell activity in HCC cells or HCC cells expressing HIF-1α by apigenin. NK cell cytotoxicity to HCC cells expressing HIF-1α was significantly increased, and NK cell-activating receptors, NKG2D, NKp30 and NKp44 were highly expressed. The activating effect of apigenin on NK cells substantially induced apoptosis in HCC cells expressing HIF-1α through high expression of CD95L on the surface of NK-92 cells. Moreover, apigenin excellently inhibited the level of TGF-β1 in a coculture of NK cells and HCC cells. In conclusion, apigenin seems to be a good compound that increases NK cell cytotoxicity to HCC cells by controlling HIF-1α expression.

• Journal of Acupuncture Research
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• v.33 no.2
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• pp.1-9
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• 2016

Objectives : I investigated whether snake venom can synergistically strengthen the cytotoxic effects of NK-92 cells, and enhance the inhibition of the growth of lung cancer cells including NCI-H358 through the induction of death receptor dependent extrinsic apoptosis. Methods : Snake venom toxin inhibited cell growth of NCI-H358 Cells and exerted non influence on NK-92 cell viability. Moreover, when they were co-cultured with NK cells and concomitantly treated with $4{\mu}g/m{\ell}$ of snake venom toxin, more influence was exerted on the inhibition of growth of NCI-H358 cells than BV or NK cell co-culture alone. Results : The expression of Fas, TNFR2 and DR3 and in NCI-H358 lung cancer cells was significantly increased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells alone. Coincidentally, Bax, caspase-3 and caspase-8 - expressions of pro-apoptotic proteins in the extrinsic apoptosis pathway, demonstrated significant increase. However, in anti-apoptotic NF-${\kappa}B$ activities, activity of the signal molecule was significantly decreased by co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells or snake venom toxin treated by NCIH358 alone. Meanwhile, in terms of NO generation, there is a significant increase, in co-culture of NK-92 cells with NCI-H358 cells as well as the co-culture of NK-92 cells and concomitant treatment of $4{\mu}g/m{\ell}$ of snake venom toxin. However, no synergistic increase of NO generation was shown in co-culture of NK-92 cells and treatment of $4{\mu}g/m{\ell}$ of snake venom toxin, compared to co-culture of NK-92 cells with NCI-H358 cells. Conclusion : Consequently, this data provides that snake venom toxin could be useful candidate compounds to suppress lung cancer growth along with the cytotoxic effect of NK-92 cells through extrinsic apoptosis.

• Journal of Ginseng Research
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• v.33 no.4
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• pp.278-282
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• 2009

The in-vitro immunomodulatory function of the activity of murine natural-killer (NK) cells induced by redginseng acidic polysaccharide (RGAP) was examined. RGAP induced the significant enhancement of NK cell activity against the Yac-1 tumor cells. The treatment of splenocytes cultured with RGAP for 16 h resulted in a significant increase in NK activity at the E:T ratio of 100:1, and in a 239 and 250% increase at 10 and $100{\mu}g$/ml, respectively. We also demonstrate that RGAP treatment increased the production of interferon (IFN)-$\gamma$ (17-125%) and tumor necrosis factor (TNF)-${\alpha}$ (15-100%), suggesting that the increase in NK cell cytotoxicity could be due to the enhancement of the NK cell production of both cytokines. In addition, RGAP had a stimulating effect on lymphocyte proliferation in the presence of mitogens. Overall, these results suggest that RGAP has an immunopotentiating effect on NK cells, which can support the development of clinical studies on RGAP.