• Title/Summary/Keyword: cell-cell interaction

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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.

LAMMER Kinase Modulates Cell Cycle by Phosphorylating the MBF Repressor, Yox1, in Schizosaccharomyces pombe

  • Kibum Park;Joo-Yeon Lim;Je-Hoon Kim;Jieun Lee;Songju Shin;Hee-Moon Park
    • Mycobiology
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    • v.51 no.5
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    • pp.372-378
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    • 2023
  • Lkh1, a LAMMER kinase homolog in the fission yeast Schizosaccharomyces pombe, acts as a negative regulator of filamentous growth and flocculation. It is also involved in the response to oxidative stress. The lkh1-deletion mutant displays slower cell growth, shorter cell size, and abnormal DNA content compared to the wild type. These phenotypes suggest that Lkh1 controls cell size and cell cycle progression. When we performed microarray analysis using the lkh1-deletion mutant, we found that only four of the up-regulated genes in the lkh1-deletion were associated with the cell cycle. Interestingly, all of these genes are regulated by the Mlu1 cell cycle box binding factor (MBF), which is a transcription complex responsible for regulating the expression of cell cycle genes during the G1/S phase. Transcription analyses of the MBF-dependent cell-cycle genes, including negative feedback regulators, confirmed the up-regulation of these genes by the deletion of lkh1. Pull-down assay confirmed the interaction between Lkh1 and Yox1, which is a negative feedback regulator of MBF. This result supports the involvement of LAMMER kinase in cell cycle regulation by modulating MBF activity. In vitro kinase assay and NetPhosK 2.0 analysis with the Yox1T40,41A mutant allele revealed that T40 and T41 residues are the phosphorylation sites mediated by Lkh1. These sites affect the G1/S cell cycle progression of fission yeast by modulating the activity of the MBF complex.

T Cell Microvilli: Finger-Shaped External Structures Linked to the Fate of T Cells

  • Hye-Ran Kim;Jeong-Su Park;Won-Chang Soh;Na-Young Kim;Hyun-Yoong Moon;Ji-Su Lee;Chang-Duk Jun
    • IMMUNE NETWORK
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    • v.23 no.1
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    • pp.3.1-3.14
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    • 2023
  • Microvilli are outer membrane organelles that contain cross-linked filamentous actin. Unlike well-characterized epithelial microvilli, T-cell microvilli are dynamic similar to those of filopodia, which grow and shrink intermittently via the alternate actin-assembly and -disassembly. T-cell microvilli are specialized for sensing Ags on the surface of Ag-presenting cells (APCs). Thus, these finger-shaped microprotrusions contain many signaling-related proteins and can serve as a signaling platforms that induce intracellular signals. However, they are not limited to sensing external information but can provide sites for parts of the cell-body to tear away from the cell. Cells are known to produce many types of extracellular vesicles (EVs), such as exosomes, microvesicles, and membrane particles. T cells also produce EVs, but little is known about under what conditions T cells generate EVs and which types of EVs are released. We discovered that T cells produce few exosomes but release large amounsts of microvilli-derived particles during physical interaction with APCs. Although much is unanswered as to why T cells use the same organelles to sense Ags or to produce EVs, these events can significantly affect T cell fate, including clonal expansion and death. Since TCRs are localized at microvilli tips, this membrane event also raises a new question regarding long-standing paradigm in T cell biology; i.e., surface TCR downmodulation following T cell activation. Since T-cell microvilli particles carry T-cell message to their cognate partner, these particles are termed T-cell immunological synaptosomes (TISs). We discuss the potential physiological role of TISs and their application to immunotherapies.

Interaction of Bone Marrow Stromal Stem Cells with Adhesive Protein and Polypeptide-adsorbed Poly(lactide-co-glycolide) Scaffolds (골수유래 간엽줄기세포와 점착성 단백질 및 폴리펩타이드가 흡착된(락티이드/글리콜라이드) 공중합체 지지체와의 상호작용)

  • Choi, Jin-San;Lee, Sang-Jin;Jang, Ji-Wook;Khang, Gil-Son;Lee, Young-Moo;Lee, Bong;Lee, Hai-Bang
    • Polymer(Korea)
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    • v.27 no.5
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    • pp.397-404
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    • 2003
  • The interaction of cell adhesive protein and polypeptide with bone marrow stromal stem cells (BMSCs) grown in tissue engineered films and scaffolds were examined. Several proteins or polypeptide known as cell-adhesive were coated adsorption on poly(lactide-co-glycolide) (PLGA) films and scaffolds and adhesion and proliferation behavior of BMSC on those surfaces were compared. The protein and polypeptide used include collagen IV, fibrinogen, laminin, gelatin, fibronectin, and poly(L-lysine). The protein and polypeptide were adsorbed on the PLGA film surfaces with almost monolayer coverage except poly(L-lysine). BMSCs were cultured for 1, 2, and 4 days on the protein- or polypeptide-adsorbed PLGA films and scaffolds. The cell adhesion and proliferation behaviors were assessed by sulforho damine B assay. It was observed that the protein- or polypeptide-adsorbed surfaces showed better cell adhesion and proliferation than the control.

Effects of Direct Cell Contact Between Monocytes and Fibroblasts on the Interleukin-6 Production and Cell Proliferation of Human Gingival and Peri - odontal Ligament Fibroblasts (치은섬유아세포와 치주인대섬유아세포의 interleukin-6 분비 및 세포성장에 미치는 단핵구세포주와 섬유아세포의 세포간 접촉작용)

  • Kim, Soo-Ah;Lee, Ho;Kim, Hyung-Seop;Oh, Kwi-Ok
    • Journal of Periodontal and Implant Science
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    • v.29 no.4
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    • pp.803-823
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    • 1999
  • In order to reveal immunopathogenesis of periodontal tissue destruction, it is important to clarify the molecular mechanism of trafficking and retention of activated leukocytes, including monocytes/macrophages. Gingival fibroblasts may be involved in the regulation of inflammatory cell accumulation in the extravascular periodontal connective tissues via cytokine production and surface expression of adhesion molecules. In this study, it was investigated the molecular basis for the adhesive interactions between monocytes and fibroblasts such as peri-odontal ligament fibroblast(PDLF), human gingival fibroblast(HGF), and human dermal fibroblast(HDF). First, it was examined the evidence whether monocyte-fibroblast cell contact may cause signal transduction in fibroblasts. Being directly in contact with fixed human monocyte cell line THP-1, or U937, upregulation of IL-6 production, $TNF-{\alpha}$ mRNA expression and increased cell proliferation could be seen for fibroblasts. IL-6 production induced by monocyte- fibroblast coculture were further increased when fibroblasts had been pretreated with $IFN-{\gamma}$ or $IL-1{\beta}$ , and monocytes with LPS. Next, it was examined the expression of ICAM-1 which has been known to be involved in accumulation and activation of leukocytes in inflammatory diseases such as periodontitis. ICAM-1 was upregulated up to 10-fold on PDLF, HGF, and HDF by exposure to $IFN-{\gamma}$ or $IL-1{\beta}$. Furthermore, anti-ICAM-1 monoclonal antibody clearly blocked cocultureinduced IL-6 production by fibroblasts, suggesting that $ICAM-1/{\beta}_2$integrin pathway is involved in periodontal fibroblastmonocyte interaction. Overall, these findings provide evidence that periodontal fibroblasts could be involved in the accumulation and retention of monocytes/macrophages in periodontal inflammatory lesion at least in part by ICAM-1 expression. In addition, periodontal fibroblast-monocyte interaction could cause activation signals in fibroblasts intracellularly which result in cytokine production and cell proliferation. Thus, periodontal fibroblasts are speculated to play an important role in immunoregulation and tissue destruction in chronic periodontal diseases by interaction with monocytes/macrophages.

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Data Modeling for Cell-Signaling Pathway Database (세포 신호전달 경로 데이타베이스를 위한 데이타 모델링)

  • 박지숙;백은옥;이공주;이상혁;이승록;양갑석
    • Journal of KIISE:Databases
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    • v.30 no.6
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    • pp.573-584
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    • 2003
  • Recent massive data generation by genomics and proteomics requires bioinformatic tools to extract the biological meaning from the massive results. Here we introduce ROSPath, a database system to deal with information on reactive oxygen species (ROS)-mediated cell signaling pathways. It provides a structured repository for handling pathway related data and tools for querying, displaying, and analyzing pathways. ROSPath data model provides the extensibility for representing incomplete knowledge and the accessibility for linking the existing biochemical databases via the Internet. For flexibility and efficient retrieval, hierarchically structured data model is defined by using the object-oriented model. There are two major data types in ROSPath data model: ‘bio entity’ and ‘interaction’. Bio entity represents a single biochemical entity: a protein or protein state involved in ROS cell-signaling pathways. Interaction, characterized by a list of inputs and outputs, describes various types of relationship among bio entities. Typical interactions are protein state transitions, chemical reactions, and protein-protein interactions. A complex network can be constructed from ROSPath data model and thus provides a foundation for describing and analyzing various biochemical processes.

Development of Polymer Electrolyte Membranes Using Dipole-dipole Interaction for Fuel Cell Applications (쌍극자-쌍극자 상호작용 형성을 이용한 향상된 기능의 연료전지용 고분자 전해질 막의 개발)

  • Won, Mihee;Kwon, Sohyun;Kim, Tae-Hyun
    • Journal of the Korean Chemical Society
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    • v.59 no.5
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    • pp.413-422
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    • 2015
  • Proton exchange membrane (PEM), which transfers proton from the anode to the cathode, is the key component of the proton exchange membrane fuel cell (PEMFC). Nafion is widely used as PEM due to its high proton conductivity as well as excellent chemical and physical stabilities. However, its high cost and the environmental hazards limit the commercial application in PEMFCs. To overcome these disadvantages, various alternative polymer electrolytes have been investigated for fuel cell applications. We used densely sulfonated polymers to maximize the ion conductivity of the corresponding membrane. To overcome high swelling, dipole-dipole interaction was used by introducing nitrile groups into the polymer backbone. As a result, physically-crosslinked membranes showed improved swelling ratio despite of high water uptake. All the membranes with different hydrophilic-hydrophobic compositions showed higher conductivity, despite their lower IEC, than that of Nafion-117.

Heat Shock Protein $90{\beta}$ Inhibits Phospholipase $C{\gamma}-1$ Activity in vitro

  • Cho, Sang-Min;Kim, Sung-Kuk;Chang, Jong-Soo
    • Biomedical Science Letters
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    • v.12 no.4
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    • pp.419-425
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    • 2006
  • Phospholipase $C-{\gamma}1\;(PLC-{\gamma}1)$ is an important signaling molecule for cell proliferation and differentiation. $PLC-{\gamma}1$ contains two pleckstrin homology (PH) domains, which are responsible for protein-protein interaction and protein-lipid interaction. $PLC-{\gamma}1$ also has two Src homology (SH)2 domains and a SH3 domain, which are responsible for protein- protein interaction. To identity proteins that specifically binds to PH domain of $PLC-{\gamma}1$, we prepared and incubated the glutathione S-transferase(GST)-fused PH domains of $PLC-{\gamma}1$ with COS7 cell lysate. We found that 90 kDa protein specifically binds to PH domain of $PLC-{\gamma}1$. By matrix-assisted laser desorption ionization time of flight-mass spectrometry, the 90 kDa protein revealed to be heat shock protein (Hsp) $90{\beta}$. Hsp $90{\beta}$ is a molecular chaperone that stabilizes and facilitates the folding of proteins that are involved in cell signaling, including receptors for steroids hormones and a variety of protein kinases. To know whether Hsp $90{\beta}$ affects on $PLC-{\gamma}1$ activity, we performed $PIP_2$ hydrolyzing activity of $PLC-{\gamma}1$ in the presence of purified Hsp $90{\beta}$ in vitro. Our results show that the Hsp $90{\beta}$ dose-dependently inhibits the enzymatic activity of $PLC-{\gamma}1$ and further suggest that Hsp $90{\beta}$ regulates cell growth and differentiation via regulation of $PLC-{\gamma}1$ activity.

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Changes in Skp2 in Helicobacter pylori-Infected Gastric Epithelial Cells (Helicobacter pylori에 감염된 위상피세포에서 Skp2의 변화)

  • Chung, Hae-Yun
    • The Korean Journal of Food And Nutrition
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    • v.25 no.1
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    • pp.64-68
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    • 2012
  • It has been suggested that Helicobacter pylori(H. pylori) infections can promote the development and progression of gastric cancer through the modulation of cell cycle regulators such as $p27^{Kip1}$ and Skp2. $p27^{Kip1}$ is a cyclin-dependent kinase (CDK) inhibitor that blocks the G1/S transition necessary for cell cycle progression. Skp2 is a component of the ubiquitin ligase complex called $SCF^{Skp2}$(SKP1-Cullin-F-box), which specifically binds and promotes the degradation of $p27^{Kip1}$. A low level of $p27^{Kip1}$ and a high level of Skp2 have been reported in many types of cancers, including gastric cancer. In addition, a decrease in $p27^{Kip1}$ has been reported in H. pylori-infected specimens. However, data on Skp2 in H. pylori infections are limited. This study examines the changes in the status of Skp2 in H. pylori-infected gastric epithelial AGS cells. For this, we stimulated AGS cells with H. pylori(NCTC 11637) at the ratio of 300:1(bacterium:cell) for 6 hours. The results of an immunoprecipitation analysis, followed by a western blot, indicate that the interaction between Skp2 and 14-3-3 was elevated 3 hours after the H. pylori treatment. In addition, there was an increase in cytoplasmic Skp2 after 3 hours, whereas there was no change in the nuclear level. Since it has been reported that interaction with 14-3-3 and the subsequent cytoplasmic translocation of Skp2 can increase its protein stability, increases in the interaction with 14-3-3 and the cytoplasmic Skp2 after the H. pylori treatment can increase the level of Skp2 in AGS cells. This phenomenon may explain, at least to some extent, the mechanism underlying the relationship between H. pylori infections and gastric carcinogenesis.

Physiological Responses of Corn Plants to Chlorsulfuron and Imazaquin (Chlorsulfuron 과 Imazaquin에 대한 옥수수의 생리적 반응)

  • Kim, K.J.;Hwang, I.T.;Choi, J.S.;Cho, K.Y.;Pyon, J.Y.
    • Korean Journal of Weed Science
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    • v.16 no.1
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    • pp.64-71
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    • 1996
  • This study was conducted to determine the physiological responses of corn plants to chlorsulfuron, CHL, (2-chloro-N-(((4-methoxy-6-methyl-1,3,5- triazin-2-yl)amino)carboxyl) benzenesulfonamide) and/or imazaquin, IMA, (2-(4,5-dihydro-4-methyl-4-(1-methyl)-5-oxo-1H-imidazol-2y1)-3-quinoline carboxylic acid). CHL inhibited the plant growth within 6h after treatment, whereas IMA inhibited the growth more slowly(i.e., 36h). CHL inhibited the cell division of the root tips rapidly, however, little effect was found with IMA treatment. Neither CHL nor IMA had effect on the cell elongation of the shoots. CHL inhibited acetolactate synthase(ALS) activity of the roots within 1h after treatment. Interaction between CHL and IMA in growth inhibition was found to be additive or synergistic with simultaneous or sequential treatment of the two herbicides, respectively. In addition, interaction between CHL and IMA in ALS inhibition was found to be additive when the two herbicides were treated simultaneously.

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