• Title/Summary/Keyword: Selectin

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Anaplasma Phagocytophilum Major Surface Protein (Msp)-2 Directly Binds to Platelet Selectin Glycoprotein Ligand-1 (CD162) Prior to Cell Entry and Infection (숙주세포 침입을 위한 Anaplasma phagocytophilum의 주요 표면단백질 (Msp)-2과 PSGL-1 (CD162)과의 반응)

  • Park Jin-Ho
    • Journal of Veterinary Clinics
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    • v.23 no.1
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    • pp.9-13
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    • 2006
  • Anaplasma phagocytophilum major surface protein-2 (Msp2 or p44) is the immunodominant outer membrane protein of the bacterium. Recently, we disclosed that Msp2 was an A. phagocytophilum adhesin for binding to host neutrophils and HL-60 cells, probably mediated by attachment to platelet selectin glycoprotein ligand-1 (PSGL-1). In this study, we further elucidated that Msp2 bound to PSGL-1/FucT IV-transfected BJAB but not nontransfected BJAB cells. Binding of recombinant Msp2 or cell (lee bacteria to the surface of PSGL-1/FucT IV-transfected BJAB cells was significantly higher than to nontransfected BJAB cells (p<0.01 and p<0.01). Also, Msp2 monoclonal antibody and soluble recombinant Msp2 as antagonist led to concentration-dependent reductions in A. phagocytophilum adhesln (p<0.05 and p<0.01) to transfected BJAB cells. Thus, we conclude that Msp2 of. A. phagocytophilum acts as an adhesin by which the bacterium binds to PSGL-1 on host neutrophils and myeloid cells.

The inhibitory activity of ginsenoside Rp4 in adenosine diphosphate-induced platelet aggregation

  • Son, Young-Min;Jeong, Da-Hye;Park, Hwa-Jin;Rhee, Man-Hee
    • Journal of Ginseng Research
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    • v.41 no.1
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    • pp.96-102
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    • 2017
  • Background: Korean ginseng, Panax ginseng Meyer, has been used as a traditional oriental medicine to treat illness and promote health for several thousand years. Ginsenosides are the main constituents for the pharmacological effects of P. ginseng. Since several ginsenosides, including ginsenoside (G)-Rg3 and G-Rp1, have reported antiplatelet activity, here we investigate the ability of G-Rp4 to modulate adenosine diphosphate (ADP)-induced platelet aggregation. The ginsenoside Rp4, a similar chemical structure of G-Rp1, was prepared from G-Rg1 by chemical modification. Methods: To examine the effects of G-Rp4 on platelet activation, we performed several experiments, including antiplatelet ability, the modulation of intracellular calcium concentration, and P-selectin expression. In addition, we examined the activation of integrin ${\alpha}IIb{\beta}_3$ and the phosphorylation of signaling molecules using fibrinogen binding assay and immunoblotting in rat washed platelets. Results: G-Rp4 inhibited ADP-induced platelet aggregation in a dose-dependent manner. We found that G-Rp4 decreased calcium mobilization and P-selectin expression in ADP-activated platelets. Moreover, fibrinogen binding to integrin ${\alpha}IIb{\beta}_3$ by ADP was attenuated in G-Rp4-treated platelets. G-Rp4 significantly attenuated phosphorylation of extracellular signal-regulated protein kinases 1 and 2, p38, and c-Jun N-terminal kinase, as well as protein kinase B, phosphatidylinositol 3-kinase, and phospholipase C-${\gamma}$ phosphorylations. Conclusion: G-Rp4 significantly inhibited ADP-induced platelet aggregation and this is mediated via modulating the intracellular signaling molecules. These results indicate that G-Rp4 could be a potential candidate as a therapeutic agent against platelet-related cardiovascular diseases.

The whole wheat effect and refined with E-selectin polymorphism on breast cancer

  • Zakariya, Bilal Fadil;Almohaidi, Asmaa M. Salih;Simsek, Secil Akilli;Kamal, Areege Mustafa;Al-Dabbagh, Wijdan H.;Al-Waysi, Safaa A.
    • Analytical Science and Technology
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    • v.35 no.4
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    • pp.161-168
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    • 2022
  • Wheat is rich in sources of fiber, oligosaccharides, and resistant starch, simple carbohydrates which may have a protective role against carcinoma. Additionally, Whole wheat/bran as well includes contains phytochemicals such as flavonoids, lignans, folate, phytosterols, phenolic acids, and tocols. The above phytochemicals suitable forms antioxidant and cholesterol-reducing activities. Phytoestrogens are regarded as especially essential in the preventative measures of hormonally dependent malignancies such as breast cancer (BC). In this study lowered BC risk has been associated with whole grain/bran consumption with an odds ratio (OR=0.24 and 95 %CI=0.10-0.56). Wheat/bran appears to have a reliable protective impact against BC. While intake of white bread has been associated with a high risk of BC (OR=2.63 and CI 95 %=1.07-6.48). Also, the E-Selectin (SELE) Single nucleotide polymorphisms (SNPs) rs5353 A/G and rs932307 C/T were investigated using the sanger sequences approach. There was a positive association between genotypes (rs5353 GG+AG) and (rs932307 TT+CT) with rate consumption of wheat-white/bread and these genotypes were more frequent in patients had BC in comparison with a significant difference (P=0.03) (P=0.01), respectively. The genotypes (GG+AG) frequency of the rs5353 polymorphism and (TT+CT) genotypes of the rs932307 polymorphism in the present study had a high risk of cancer with (OR=3.05), (OR=4.17) respectively. While these genotypes showed no significant association with the rate of whole grain consumption in patients and control. Therefore, the type of wheat may associate with increased incidence of disease-related with type of Polymorphism because some present genotypes of SNPs showed high (OR) which may refer to their positive associated with disease, the white wheat consumption may active the risky association between SNPs and BC.

Fusobacterium nucleatum GroEL signaling via Toll-like receptor 4 in human microvascular endothelial cells

  • Lee, Hae-Ri;Choi, Bong-Kyu
    • International Journal of Oral Biology
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    • v.37 no.3
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    • pp.130-136
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    • 2012
  • The GroEL heat-shock protein from Fusobacterium nucleatum, a periodontopathogen, activates risk factors for atherosclerosis in human microvascular endothelial cells (HMEC-1) and ApoE-/- mice. In this study, we analyzed the signaling pathways by which F. nucleatum GroEL induces the proinflammatory factors in HMEC-1 cells known to be risk factors associated with the development of atherosclerosis and identified the cellular receptor used by GroEL. The MAPK and NF-${\kappa}B$ signaling pathways were found to be activated by GroEL to induce the expression of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and tissue factor (TF). These effects were inhibited by a TLR4 knockdown. Our results thus indicate that TLR4 is a key receptor that mediates the interaction of F. nucleatum GroEL with HMEC-1 cells and subsequently induces an inflammatory response via the MAPK and NF-${\kappa}B$ pathways.

Antioxidant and Anti-inflammatory Activities of Allium victorialis subsp. platyphyllum Extracts

  • Lee, Je-Hyuk;Choi, Soo-Im;Lee, Yong-Soo;Kim, Gun-Hee
    • Food Science and Biotechnology
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    • v.16 no.5
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    • pp.796-801
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    • 2007
  • This study was conducted to investigate antioxidant activity and anti-immunological inflammatory effect of Allium victorialis subsp. platyphyllum extracts (AVPEs). Antioxidant activities of AVPEs were determined by free radical scavenging assay and reducing power test. Leaf-part extract had comparatively better antioxidant activity than other-part extracts. Antioxidant activity of extracts had protective effect for human umbilical vein endothelial cells (HUVECs) against superoxide anions secreted from activated neutrophils. Also, we observed AVPEs had inhibitory effects on the adherence of monocytic THP-1 to HUVEC monolayer to the basal level. Inhibitory effect on cell adhesion was caused by suppression of tumor necrosis factor-${\alpha}\;(TNF-{\alpha})-upregulated$ expression of vascular cellular adhesion molecule-1 (VCAM-1) and E-selectin in HUVECs. From these results, we expect to support the evidence of anti-immunological inflammatory effects of Allium victorialis subsp. platyphyllum (AVP) as a Korean traditional pharmaceutical.

Binding of Galectin-1 to Neutrophils Enhanced by Activation

  • Cho, Somi K.;Cho, Moonjae
    • Journal of Applied Biological Chemistry
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    • v.43 no.3
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    • pp.131-135
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    • 2000
  • Human polymorphonuclear neutrophils undergo diaphoresis after a selectin-mediated rolling on the endothelial cells of the blood vessel wall. Extravasation is believed to be an integrin-mediated process. Galectin-1 is a small dimeric beta-galactoside-binding protein synthesized by the endotherial cells and present in the perivascular connective tissue. In this study we suggest the possible role of galectin-1 in extravasation of the activated neutrophils. MAL lectin binding study showed, that f-MetLeuPhe-activated neutrophils decrease surface sialylation and increase galectin-1 binding via exposure of new galectin-1 binding sites. Desialylated HL-60 cells also show the same decrease in MAL binding and increase in galectin-1 binding, an increase which was not observed in the presence of lactose. Galectin-1 blotting analysis detected two possible major ligands (approximately 120 and 160 kDa) of galectin-1 from the desialylated HL-60 cell lysates.

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Selection and Mechanism of Anti-Obesity Agents from Natural Products Based on Anti-Angiogenesis (신생혈관형성억제작용을 기반으로 한 항비만제제의 선별 및 작용기전)

  • Shin, Jin-Hyuk;Lee, Jin-Hee;Kang, Kyeong-Wan;Hwang, Jae-Ho;Han, Kyeong-Ho;Shin, Tai-Sun;Kim, Min-Yong;Kim, Jong-Deog
    • KSBB Journal
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    • v.24 no.2
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    • pp.122-130
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    • 2009
  • Anti-angiogenic mechanism was examined for anti-obesity agents with the extract of P.radix, P.semen, S.hebra and C.furctus through anti-cell adhesion effect and western blot. Cell adhesion molecules, VCAM-1 was supressed with the order of P.radix (0.2 ppm, 125%) > P.semen (0.5 ppm, 100%) > S.hebra (5.0 ppm, 114%) > C. furctus (5.0 ppm, 111.8%), ICAM-1 was inhibited by P.radix (0.25 ppm, 130%) > P.semen (0.5 ppm, 100%) > S.hebra (5.0 ppm, 138%) > C. furctus (5.0 ppm, 66.7%), E-Selectin was also supressed P.radix (0.25 ppm, 100%) > P.semen (1.0 ppm, 128%) > S.hebra (5.0 ppm, 120%) > C. furctus (5.0 ppm, 100.7%). And signal molecules, VE-cadherin was supressed by P.radix and S.hebra, ${\beta}$-catenin was inhibited by P.radix, and Akt was supressed all these 4 kinds of natural products. These P.radix, P.semen, S.hebra and C.furctus were showed the possibility of anti-obesity agents based on anti-angiogenesis.

Anti-Angiogenic and Anti-Cell Adhesion Effect of the Camellia japonica Flower Extract (동백꽃 추출물의 신생혈관생성 및 세포부착 억제 효과)

  • Heo, In-Do;Seo, Hyo-Jin;Kim, Jong-Deog
    • Journal of Life Science
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    • v.17 no.8 s.88
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    • pp.1152-1156
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    • 2007
  • The Camella japonica flower(CJF) extract was studied for their anti-angiogenenic and anti-cell adhesion effect. CJF-extract inhibited the tube formation on human umbilical vein endotherial cells(HUVEC) with butanol extract by 70.2%, acetone extract by 54.2%, ethyl acetate extract by 37.0%, chloroform extract by 21.2%. Cell adhesion molecules were effectively suppressed at different concentration of CJF at 50, 100, 200 ug/well such as for intercellular adhesion molecule(ICAM) by 5.9%, 29.4% and 52.9%, for vascular cell adhesion molecule(VCAM) by 12.5%, 43.8% and 62.5%, for E-selectin by 7.1%, 21.4% and 35.7%, respectively. Signal molecules of vascular endotherial growth factor receptor 2(VEGFR2), ${/beta}$-catenin and PI3K are inhibited by different concentration of CJF at 10, 20 and 30 ${\mu}g/mL$ with western blot. Angiogenesis will be inhibited with suppressing NF-kB molecule resulted in signal molecules blocked by CJF. CJF will be useful materials for treatment of angiogenesis related diseases such as cancer, metastasis, rheumathioid arthritis and obesity.

Microarray Analysis of Gene Expression Profile by Treatment of Schizandrae fructus Extract in Inflammation-induced Human Epithelial A549 Cells (염증이 유발된 인간기관지상피세포에서 오미자가 Microarray를 이용한 유전자 발현 분석에 미치는 영향)

  • Jung, Jin-Yong;Jung, Sung-Ki;Jung, Hee-Jae;Rhee, Hyung-Koo
    • The Journal of Internal Korean Medicine
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    • v.29 no.3
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    • pp.543-553
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    • 2008
  • Objective: The goal of this study was to determine the anti-asthma mechanism of SF on TNF-${\alpha}$ induced activation on A549 (human type II-like epithelial) cells. Using oligonucleotide microarray, we sought to establish the molecular mechanism of the protective effects of SF on A549 cells. Material & Methods : Cells were cultured in three different conditions: 1) negative control group was cultured in normal condition of DMEM, 2) positive control group was activated with TNF-${\alpha}$, IL-4. and IL-1${\beta}$, and 3) SF treated group was previously treated with 0.1${\mu}g/ml$ SF after TNF-${\alpha}$, IL-4. and IL-1 activation. Cells of positive control and SF treated groups were cultured for 30 min, 1hr, 3hr and 6hr. Results : The comparative analysis of the gene expression profile revealed that proinflammatory cytokines such as IL1F8, IL1F9, IL1R1. IL1RN, IL1RAPL1, IL8, TNFRSF4, TNFSF10c, TNFSF13, TRAF5, and TRAF7 and inflammation-related genes including MMP2, MMP11, MMP14, MMP15, MMP16, MMP19, MMP25, and MMP27 were down regulated with SF treatment. Cell adhesion molecule genes such as ITGB1, ITGBL1, selectin P ligand, selectin E, ICAM2, ICAM3, VCAM1, PECAM, FCER1G and MMP28 genes were also down-regulated in SF treated A549 cells. Conclusion : These results suggest that the anti-asthmatic effects of SF could be mediated by regulating specific genes related with cell adhesion, proinflammatory cytokine and inflammation-related genes in A549 cells.

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Inhibition Effect of Enzymatic Hydrolysate from Japanese Mud Shrimp Upogebia major on TNF-α-induced Vascular Inflammation in Human Umbilical Vein Endothelial Cells (HUVECs) (혈관내피세포에서 TNF-α로 유도되는 혈관염증에 대한 쏙(Upogebia major) 효소가수분해물의 억제 효과)

  • Kim, So-Yeon;Yang, Ji-Eun;Song, Jae-Hee;Maeng, Sang-Hyun;Lee, Ji-Hyun;Yoon, Na-Young
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.51 no.2
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    • pp.127-134
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    • 2018
  • Arteriosclerosis is the major cause of coronary artery and cerebrovascular disease, which are leading causes of death. Pro-inflammatory cytokines induce injury to vascular endothelial cells by increasing cell adhesion molecules, leading to vascular inflammation, a major risk factor for the development of arteriosclerosis. In the current study, we investigated the inhibitory effect of enzymatic hydrolysate from Japanese mud shrimp Upogebia major on the inflammation of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$)-stimulated human umbilical vein endothelial cells (HUVECs). We first evaluated the antioxidant and angiotensin I-converting enzyme (ACE) inhibitory activities of eight U. major enzymatic hydrolysates: alcalase, papain, ${\alpha}$-chymotrypsin (${\alpha}-Chy$), trypsin, pepsin, neutrase, protamex and flavourzyme. Of these, ${\alpha}-Chy$ exhibited potent antioxidant and ACE inhibitory activities. The ${\alpha}-Chy$ hydrolysate was fractionated by two ultrafiltration membranes of 3 and 10 kDa. The ${\alpha}-Chy$ hydrolysate of U. major and its molecular weight cut-off fractions resulted in a significant reduction in NO production and a decrease in cell adhesion molecules [vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and endothelial-selectin (E-selectin)] and pro-inflammatory cytokines [interleukin-6 (IL-6), interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1)] in $TNF-{\alpha}$-stimulated HUVECs. These results suggest that enzymatic hydrolysate from U. major can be used in the control and prevention of vascular inflammation and arteriosclerosis.