• Journal of Acupuncture Research
• /
• 제34권1호
• /
• pp.1-9
• /
• 2017

Objectives : We investigated the synergistic effects of bee venom (BV) and natural killer (NK) cells on B16F10 melanoma cell apoptosis mediated by IL-4. Methods : We performed a cell viability assay to determine whether BV can enhance the inhibitory effect of NK-92MI cells on the growth of B16F10 melanoma cells, and western blot analysis to detect changes in the expression of IL-4, $IL-4R{\alpha}$, and other apoptosis-related proteins. EMSA was performed to observe the activity of STAT6. To confirm that the inhibitory effect of BV and NK cells was mediated by IL-4, the above tests were repeated after IL-4 silencing by siRNA (50 nM). Results : B16F10 melanoma cells co-cultured with NK-92MI cells and simultaneously treated by BV ($5{\mu}g/ml$) showed a higher degree of proliferation inhibition than when treated by BV ($5{\mu}g/ml$) alone or co-cultured with NK-92MI cells alone. Expression of IL-4, $IL-4R{\alpha}$, and that of other pro-apoptotic proteins was also enhanced after co-culture with NK-92MI cells and simultaneous treatment with BV ($5{\mu}g/ml$). Furthermore, the expression of anti-apoptotic bcl-2 decreased, and the activity of STAT6, as well as the expression of STAT6 and p-STAT6 were enhanced. IL-4 silencing siRNA (50 nM) in B16F10 cells, the effects of BV treatment and NK-92MI co-culture were reversed. Conclusion : These results suggest that BV could be an effective alternative therapy for malignant melanoma by enhancing the cytotoxic and apoptotic effect of NK cells through an IL-4-mediated pathway.

• 한국군사과학기술학회지
• /
• 제27권1호
• /
• pp.107-115
• /
• 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.

• 대한의생명과학회지
• /
• 제2권2호
• /
• pp.211-222
• /
• 1996

수태기간중 태아가 모체에 의해 면역학적으로 거부반응을 일으키지 않고 동종이식 상태로 유지되는 기작을 밝히는 연구의 일환으로 C3H/HeJ계의 암컷 생쥐와 DBA/2계의 수컷 생쥐를 교배하여 모체에서 발생되는 체계적인 면역기능 및 국소적 면역기능현상에 대하여 연구하고자 수태기 간별로 비 장 및 자궁으로 들어가는 림프절에서 T세포 및 B세포의 아형을 측정하였고 자연살해 세포의 활성도를 측정하였다. 또한 수태혈청 및 수태성 호르몬이 자연살해세포의 활성도에 미치는 영향을 알아보았다. 각 수태기간별로 비장세포에 있어서 T세포와 B세포의 아형을 관찰한 결과, Thy-1.2$^{+}$세포는 수태기간중 중기 이후에 감소하기 시작하여 수태 4기에는 대조군에 비하여 유의하게 감소하였으며 수태말기에는 회복하였다. L3T4$^{+}$세포도 Thy-1.2$^{+}$ 세포와 비교하여 비슷한 경향으로 감소 또는 증가하였다. Ly2$^{+}$세포는 수태중기 이후부터 대조군에 비하여 유의하게 증가하였으며 B세포는 수태중기 이후부터 수태말기까지 계속 증가하였다. 비장에 있어서 자연살해세포의 세포독성은 수태 5일에서 수태 8일 사이에 가장 증가하였으며 그 이후는 대조군 수준으로 감소하였다. 정상혈청 및 수태혈청의 자연살해세포의 세포독성에 대한 영향을 수태시기별로 조사한 결과, 정상혈청과 수태혈청 모두 자연살해세포의 세포독성을 유의하게 억제하였으며, Progesterone은 시험관내실험과 생체내 실험 모두 약리적인 농도이상에서 농도에 의존적으로 자연살해세포의 세포독성을 증가시켰으며, HCG는 5 unit/ml에서 5000 unit/ml까지 처리농도에 비례하여 자연살해세포의 세포독성을 억제하였다. 자궁으로 들어가는 림프절에서 T세포의 아형은 Thy-1.2$^{+}$세포는 수태 2기부터 증가하여 대조군에 보다 유의하게 증가하였으며, L3T4$^{+}$세포의 유의한 변화없이 Ly2$^{+}$세포가 수태 2기 이후부터 대조군에 비하여 유의하게 증가하였고 분만 직전에는 조금 감소하였다. 자궁으로 들어가는 림프절에서의 자연살해세포의 세포독성은 착상직후 대조군에 비하여 유의하게 증가하였으며, 수태중기와 수태후기에도 대조군에 비하여 세포독성이 증가하였으며, 같은 시기의 비장세포의 자연살해세포의 세포독성보다 높게 나타났다.

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

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권12호
• /
• pp.7335-7338
• /
• 2013

There is increasing evidence that natural killer (NK) cells play an important role in antitumor immunity following dendritic cell (DC) vaccination. Little is known, however, about the optimal stimulation of DCs by epitopes and NK interactions for cytotoxicity in tumors. In this study, DC cells activated by the HPV16E7.49-57 epitope and LPS were co-cultured with NK cells in vitro, and then used ot immunize mice to study CTL activity of TC-1, which constitutively expresses HPV16E6E7, with an LDH release assay. Cytotoxicity in mice immunized with DC loaded with epitope HPVE7.49-57 vaccine co-cultured with NK was enhanced significantly (p<0.01). In conclusion, talk-across between DC and NK cells enhances their functions, also improving cytotoxicity againsttumor cells, suggesting that activated DC-NK by epitopes has potential application for cancer-specific immuno-cellular therapy.

• BMB Reports
• /
• 제52권9호
• /
• pp.554-559
• /
• 2019

Despite reports suggesting that tissue-resident natural killer (trNK) cells cause ischemic kidney injury, their contribution to the development of tubulointerstitial fibrosis has not been determined. This study hypothesized that the depletion of trNK cells may ameliorate renal fibrosis by affecting transglutaminase 2/syndecan-4 interactions. Aristolochic acid nephropathy (AAN) was induced in C57BL/6 mice as an experimental model of kidney fibrosis. The mice were treated with anti-asialo GM1 (ASGM1) or anti-NK1.1 antibodies to deplete NK cells. Although both ASGM1 and NK1.1 antibodies suppressed renal $NKp46^+DX5^+$ NK cells, renal $NKp46^+DX5^-$ cells were resistant to suppression by ASGM1 or NK1.1 antibodies during the development of tubulointerstitial fibrosis in the AAN-induced mouse model. Western blot analysis showed that both antibodies increased the expression of fibronectin, transglutaminase 2, and syndecan-4. These findings indicate that trNK cells played an exacerbating role in tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in the AAN-induced mouse model.

• Archives of Pharmacal Research
• /
• 제15권1호
• /
• pp.20-29
• /
• 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.

• Clinical and Experimental Reproductive Medicine
• /
• 제38권3호
• /
• pp.119-125
• /
• 2011

Implantation of an embryo occurs during the mid-secretory phase of the menstrual cycle, known as the "implantation window." During this implantation period, there are significant morphologic and functional changes in the endometrium, which is followed by decidualization. Many immune cells, such as dendritic and natural killer (NK) cells, increase in number in this period and early pregnancy. Recent works have revealed that antigen-presenting cells (APCs) and NK cells are involved in vascular remodeling of spiral arteries in the decidua and lack of APCs leads to failure of pregnancy. Paternal and fetal antigens may play a role in the induction of immune tolerance during pregnancy. A balance between effectors (i.e., innate immunity and helper T [Th] 1 and Th17 immunity) and regulators (Th2 cells, regulatory T cells, etc.) is essential for establishment and maintenance of pregnancy. The highly complicated endocrine-immune network works in decidualization of the endometrium and at the fetomaternal interface. We will discuss the role of immune cells in the implantation period and during early pregnancy.

• Journal of Microbiology and Biotechnology
• /
• 제32권4호
• /
• pp.397-404
• /
• 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.

• The Korean Journal of Pain
• /
• 제31권1호
• /
• pp.43-49
• /
• 2018

Background: Chronic pain reportedly exerts complex effects on immune function. Natural killer (NK) cells are lymphocytes that play a critical role in cellular and innate immunity. This study examined changes in the subset populations and cytotoxic activity of peripheral blood NK cells in patients with chronic pain. Methods: Thirty patients with chronic moderate-to-severe pain (group P) and age-matched pain-free subjects (group NoP) were enrolled. Peripheral whole blood was analyzed for the percentage and expression of NK cell surface markers (CD56 and CD16) by flow cytometry. Cytotoxic activity was assayed by evaluating CD69 expression on $CD3^-/CD56^+NK$ cells. Results: The percentage of NK cells among total lymphocytes was not significantly different between groups P and NoP ($16.3{\pm}9.3$ vs. $20.2{\pm}10.5%$). Likewise, the percentages of two major NK cell subsets, $CD56^{bright}$ and $CD56^{dim}$, were also not significantly different between the two groups. However, the percentage of $CD56^{bright}/CD16^+$ subset, was slightly but significantly increased in group P ($1.0{\pm}0.9%$; P< 0.01) compared with group NoP ($0.5{\pm}0.6%$). The cytotoxicity of NK cells was not different between the two groups, showing similar CD69 expression (P vs. $NoP=29.2{\pm}15.2$ vs. $32.0{\pm}15.0%$). These findings were not influenced by pain intensity, opioid use, or disease causing pain in group P. Conclusions: NK cell cytotoxic activity and major subset populations, with the exception of an increased percentage of the $CD56^{bright}/CD16^+$ subset, are not significantly altered in patients with chronic severe pain.