• Title/Summary/Keyword: NKP

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NK cell-activating receptor NKp46 does not participate in the development of obesity-induced inflammation and insulin resistance

  • Gracia Nathalie;Beatriz Dal Santo Francisco Bonamichi;Jieun Kim;Jiwon Jeong;Haneul Kang;Emirrio Reinaldie Hartland;Eveline Eveline;Jongsoon Lee
    • Molecules and Cells
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    • v.47 no.3
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    • pp.100007.1-100007.11
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    • 2024
  • Recent evidence establishes a pivotal role for obesity-induced inflammation in precipitating insulin resistance and type-2 diabetes. Central to this process is the proinflammatory M1 adipose-tissue macrophages (ATMs) in epididymal white adipose tissue (eWAT). Notably, natural killer (NK) cells are a crucial regulator of ATMs since their cytokines induce ATM recruitment and M1 polarization. The importance of NK cells is shown by the strong increase in NK-cell numbers in eWAT, and by studies showing that removing and expanding NK cells respectively improve and worsen obesity-induced insulin resistance. It has been suggested that NK cells are activated by unknown ligands on obesity-stressed adipocytes that bind to NKp46 (encoded by Ncr1), which is an activating NK-cell receptor. This was supported by a study showing that NKp46-knockout mice have improved obesity-induced inflammation/insulin resistance. We therefore planned to use the NKp46-knockout mice to further elucidate the molecular mechanism by which NKp46 mediates eWAT NK-cell activation in obesity. We confirmed that obesity increased eWAT NKp46+ NK-cell numbers and NKp46 expression in wild-type mice and that NKp46-knockout ablated these responses. Unexpectedly, however, NKp46-knockout mice demonstrated insulin resistance similar to wild-type mice, as shown by fasting blood glucose/insulin levels and glucose/insulin tolerance tests. Obesityinduced increases in eWAT ATM numbers and proinflammatory gene expression were also similar. Thus, contrary to previously published results, NKp46 does not regulate obesity-induced insulin resistance. It is therefore unclear whether NKp46 participates in the development of obesity-induced inflammation and insulin resistance. This should be considered when elucidating the obesity-mediated molecular mechanisms that activate NK cells.

Korean Red Ginseng modulates immune function by upregulating CD4+CD8+ T cells and NK cell activities on porcine

  • Md Jahangir Alam;Mohammad Amjad Hossain;Kiran D. Bhilare;Chang-Won Kang;Jong-Hoon Kim
    • Journal of Ginseng Research
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    • v.47 no.1
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    • pp.155-158
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    • 2023
  • In the present study, we investigated whether treatment with KRG improve the parameters of immune activity such as the cytotoxicity, populations of CD4+ CD8+T cell, CD3-CD172-CD8+ NK cell and CD172+ monocyte as well as natural cytotoxicity receptors such as Nkp46, Nkp44, Nkp30. In results, KRG significantly increased these immune activities. These results indicate that KRG has distinct immuneenhancing effects by increasing the roles of T cells and NK cell in porcine.

Geographical Variations and Genetic Distances of Three Saxidomus purpuratus Populations ascertained by PCR Analysis

  • Yoon, Jong-Man
    • Development and Reproduction
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    • v.19 no.4
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    • pp.259-264
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    • 2015
  • Genomic DNA samples isolated from geographical purplish Washington clam (Saxidomus purpuratus) were obtained from three different regions in the Korean Peninsula: Geoje (Geoje population; GJP), Gunsan (Gunsan population; GSP) and a site of North Korea (North Korea population; NKP). The seven primers generated the total 369 loci that can be scored from the GSP clam population. 356 fragments were generated from the NKP clam population. The complexity of the banding patterns varies dramatically between the primers and three localities. In this study, 319 loci were identified in the purplish Washington clam from Geoje and 369 in the clam population from Gunsan: 221 specific loci (69.3%) in the GJP clam population and 300 (81.3%) in the GSP population. These results demonstrate that the primer detected a large quantity of specific fragments, suggesting that the genetic variation in the GSP is higher than in the GJP population. In particular, the BION-28 primer gave DNA profiles with more fragments than the other six primers in the NKP population. The oligonucleotides primer BION-75 produced 21 unique loci to each population, which were ascertaining each population, approximately 250 bp, 300 bp and 400 bp, in the GJP population. Outstandingly, the primer BION-50 detected 21 shared loci by the three populations, major and/or minor fragments of sizes 150 bp, which were matching in all samples. With regard to average bandsharing value (BS) results, individuals from GJP population (0.743) displayed higher bandsharing values than did individuals from GSP population (0.606). In the present study, the dendrogram gained by the seven oligonucleotides primers indicates three genetic clusters: cluster 1 (GEOJE 01 ~ GEOJE 07), cluster 2 (GUNSAN 08 ~ GUNSAN 14), cluster 3 (N.KOREA 15 ~ N.KOREA 21). Among the twenty one clams, the shortest genetic distance that revealed significant molecular differences was between individuals 08 and 09 from the NKP population (genetic distance = 0.073), while the longest genetic distance among the twenty-one individuals that demonstrated significant molecular differences was between individuals GEOJE no. 03 and GUNSAN no. 09 (genetic distance = 0.669). Comparatively, individuals of GJP population were properly closely related to that of NKP population, as revealed in the hierarchical dendrogram of genetic distances. In due course, PCR analysis has revealed the significant genetic distance among three purplish Washington clam populations. PCR fragments discovered in this study could be valuable as a DNA marker of the three geographical clam populations to distinguish.

Real-time Control of Biological Animal Wastewater Treatment Process and Stability of Control Parameters (생물학적 축산폐수 처리공정의 자동제어 방법 및 제어 인자의 안정성)

  • Kim, W.Y.;Jung, J.H.;Ra, C.S.
    • Journal of Animal Science and Technology
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    • v.46 no.2
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    • pp.251-260
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    • 2004
  • The feasibility and stability of ORP, pH(mV) and DO as a real-time control parameter for SBR process were evaluated in this study. During operation, NBP(nitrogen break point) and NKP(nitrate knee point), which reveal the biological and chemical changes of pollutants, were clearly observed on ORP and pH(mV)-time profiles, and those control points were easily detected by tracking the moving slope changes(MSC). However, when balance of aeration rate to loading rate, or to OUR(oxygen uptake rate), was not optimally maintained, either false NBP was occurred on ORP and DO curves before the appearance of real NBP or specific NBP feature was disappeared on ORP curve. Under that condition, however, very distinct NBP was found on pH(mV)-time profile, and stable detection of that point was feasible by tracking MSC. These results might mean that pH(mV) is superior real-time control parameter for aerobic process than ORP and DO. Meanwhile, as a real-time control parameter for anoxic process, ORP was very stable and more useful parameter than others. Based on these results, a stable real-time control of process can be achieved by using the ORP and pH(mv) parameters in combination rather than using separately. A complete removal of pollutants could be always ensured with this real-time control technology, despite the variations of wastewater and operation condition, as well as an optimization of treatment time and capacity could be feasible.

Apigenin Increases Natural Killer Cytotoxicity to Human Hepatocellular Carcinoma Expressing HIF-1α through High Interaction of CD95/CD95L

  • Lee, Hwan Hee;Cho, Hyosun
    • 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.

Cytotoxicity of natural killer cells on canine mammary carcinoma cells (개 유선종양세포에 대한 자연살해세포 독성)

  • Jeong, Da-Un;Byeon, Jeong Su;Gu, Na-Yeon;Jung, Moonhee;Kim, Eun Hee;Kim, Hyung-Seok;Cho, In-Soo;Song, Jae-Young;Hyun, Bang-Hun;Lee, Jienny
    • Korean Journal of Veterinary Research
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    • v.60 no.1
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    • pp.25-32
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    • 2020
  • Natural killer (NK) cells play have a crucial role in the early phase of immune responses against various pathogens. We compared characteristics of canine NK cells against two canine mammary carcinoma cell lines, REM134 and CF41.Mg. REM134 showed higher expression of progesterone receptor, proliferative cell nuclear antigen, Ki67, multiple drug resistance, Bmi-1, c-myc, E-cadherin, and human epidermal growth factor receptor type-2 than that of CF41.Mg. For specific expansion and activation of NK cells, we isolated CD5 negative cells from canine peripheral blood mononuclear cells and co-cultured K562 cells in the presence of interleukin (IL)-2, IL-15, and IL-21 for 21 days. As a result, we found that expression markers of activated NK cells such as NKp30, NKp44, NKp46, NKG2D, CD244, perforin, granzyme B, and tumor necrosis factor alpha were highly upregulated. In addition, we found there was upregulated production of interferon gamma of activated NK cells against target cells such as REM134 and CF41.Mg. Specifically, we observed that cytotoxicity of NK cells against target cells was more sensitively reacted to CF41.Mg than REM134. Based on the results of this study, we recommend the development of an experimental application of CF41Mg, which has not been reported in canine mammary carcinoma research.

Tissue-resident natural killer cells exacerbate tubulointerstitial fibrosis by activating transglutaminase 2 and syndecan-4 in a model of aristolochic acid-induced nephropathy

  • Wee, Yu Mee;Go, Heounjeong;Choi, Monica Young;Jung, Hey Rim;Cho, Yong Mee;Kim, Young Hoon;Han, Duck Jong;Shin, Sung
    • BMB Reports
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    • v.52 no.9
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    • pp.554-559
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    • 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.

The Natural Killer Cell Response to HCV Infection

  • Ahlenstiel, Golo
    • IMMUNE NETWORK
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    • v.13 no.5
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    • pp.168-176
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    • 2013
  • In the last few years major progress has been made in better understanding the role of natural killer (NK) cells in hepatitis C virus (HCV) infection. This includes multiple pathways by which HCV impairs or limits NK cells activation. Based on current genetic and functional data, a picture is emerging where only a rapid and strong NK cell response early on during infection which results in strong T cell responses and possible subsequent clearance, whereas chronic HCV infection is associated with dysfunctional or biased NK cells phenotypes. The hallmark of this NK cell dysfunction is persistent activation promoting ongoing hepatitis and hepatocyte damage, while being unable to clear HCV due to impaired IFN-${\gamma}$ responses. Furthermore, some data suggests certain chronically activated subsets that are $NKp46^{high}$ may be particularly active against hepatic stellate cells, a key player in hepatic fibrogenesis. Finally, the role of NK cells during HCV therapy, HCV recurrence after liver transplant and hepatocellular carcinoma are discussed.

A Study on the Numerical Simulation of the Seismic Sea Waves in the East Sea based on the Boussinesq Equation (Boussinesq 방정식을 이용한 동해지진해일 수치실험 연구)

  • Kim, Sung-Dae;Jung, Kyung-Tae;Park, Soo-Young
    • Ocean and Polar Research
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    • v.29 no.1
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    • pp.9-31
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    • 2007
  • Most seismic sea waves in the East Sea originate from earthquakes occurring near the Japanese west coast. While the waves propagate in the East Sea, they are deformed by refraction, diffraction and scattering. Though the Boussinesq equation is most applicable for such wave phenomena, it was not used in numerical modelling of seismic sea waves in the East Sea. To examine characteristics of seismic sea waves in the East Sea, numerical models based on the Boussinesq equation are established and used to simulate recent tsunamis. By considering Ursell parameter and Kajiura parameter, it is proved that Boussinesq equation is a proper equation for seismic sea waves in the East Sea. Two models based on the Boussinesq equation and linear wave equation are executed with the same initial conditions and grid size ($1min{\times}1min$), and the results are compared in various respects. The Boussinesq equation model produced better results than the linear model in respect to wave propagation and concentration of wave energy. It is also certified that the Boussinesq equation model can be used for operational purpose if it is optimized. Another Boussinesq equation model whose grid size is $40sec{\times}30sec$ is set up to simulate the 1983 and 1993 tsunamis. As the result of simulation, new propagation charts of 2 seismic sea waves focused on the Korean east coast are proposed. Even though the 1983 and 1993 tsunamis started at different areas, the propagation paths near the Korean east coast are similar and they can be distinguished into 4 paths. Among these, total energy and propagating time of the waves passing over North Korea Plateau(NKP) and South Korea Plateau(SKP) determine wave height at the Korean east coast. In case of the 1993 tsunami, the wave passing over NKP has more energy than the wave over SKP. In case of the 1983 tsunami, the huge energy of the wave passing over SKP brought about great maximum wave heights at Mukho and Imwon. The Boussinesq equation model established in this study is more useful for simulation of seismic sea waves near the Korean east coast than it is the Japanese coast. To improve understanding of seismic sea waves in shallow water, a coastal area model based on the Boussinesq equation is also required.

Anti-herpes Activity of Vinegar-processed Daphne genkwa Flos Via Enhancement of Natural Killer Cell Activity

  • Uyangaa, Erdenebileg;Choi, Jin Young;Ryu, Hyung Won;Oh, Sei-Ryang;Eo, Seong Kug
    • IMMUNE NETWORK
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    • v.15 no.2
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    • pp.91-99
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    • 2015
  • Herpes simplex virus (HSV) is a common causative agent of genital ulceration and can lead to subsequent neurological disease in some cases. Here, using a genital infection model, we tested the efficacy of vinegar-processed flos of Daphne genkwa (vp-genkwa) to modulate vaginal inflammation caused by HSV-1 infection. Our data revealed that treatment with optimal doses of vp-genkwa after, but not before, HSV-1 infection provided enhanced resistance against HSV-1 infection, as corroborated by reduced mortality and clinical signs. Consistent with these results, treatment with vp-genkwa after HSV-1 infection reduced viral replication in the vaginal tract. Furthermore, somewhat intriguingly, treatment of vp-genkwa after HSV-1 infection increased the frequency and absolute number of $CD3^-NK1.1^+NKp46^+$ natural killer (NK) cells producing interferon (IFN)-${\gamma}$ and granyzme B, which indicates that vp-genkwa treatment induces the activation of NK cells. Supportively, secreted IFN-${\gamma}$ was detected at an increased level in vaginal lavages of mice treated with vp-genkwa after HSV-1 infection. These results indicate that enhanced resistance to HSV-1 infection by treatment with vp-genkwa is associated with NK cell activation. Therefore, our data provide a valuable insight into the use of vp-genkwa to control clinical severity in HSV infection through NK cell activation.