• Journal of Marine Bioscience and Biotechnology
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• v.1 no.3
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• pp.156-162
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• 2006

The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/mL$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited non-activated U937 monocytic cell adhesion to HUVECs activated with IL-$1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with IL-$1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to IL-$1{\beta}$ stimulated HUVECs was completely suppressed by 121% at a concentration of 18.5 ug/mL. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin and VE-cadherin to NF-kB based on western bolt analysis. And also inhibited IL-1-stimulated HUVEC expression of the adhesion molecules, ICAM-1 by 40%, VCAM-1 by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities and non-toxicity may be expected from these results.

• Journal of Microbiology and Biotechnology
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• v.16 no.10
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• pp.1544-1553
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• 2006

The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/ml$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited cell adhesion that non-activated U937 monocytic cell adhesion to HUVECs activated with $IL-1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with $IL-1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to $IL-1{\beta}$-stimulated HUVECs was completely suppressed by 121% at a concentration of $18.5{\mu}g/ml$. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin, and VE-cadherin to NF-kB, based on western bolt analysis. It also inhibited IL-l-stimulated HUVEC expression of the adhesion molecules, ICAM-l by 40%, VCAM-l by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities, and non-toxicity may be expected from these results.

• IMMUNE NETWORK
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• v.1 no.1
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• pp.87-94
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• 2001

Background: Cytokine-mediated ex vivo expansion has been proposed as a means of increasing the number of cord blood (CB) hematopoietic stem cells for transplantation. As well as stem cell number, stromal cells are necessary for functional maturation of hematopoiesis. The purpose of this study was to analyze the development of stromal cells during ex vivo expansion of CB $CD34^+$ cells. Methods : $CD34^+$ cells were purified from CB by magnetic bead selection. The levels of of interleukin-3, interleukin-$1{\beta}$, interleukin-6, granulocyte macrophagecolony stimulating factor and tumor necrosis factor-${\alpha}$ were measured in culture supernatants on 0, 1, 2, and 3 weeks, using ELISA techniques. CB $CD34^+$ cells were expanded in Iscoves modified Dulbeccos medium in the presence of several cytokines. The expression of E-selectin, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, platelet/endothelial cell adhesion molecule-1, von Willebrand factor, vimentin, and CD14 in newly developed stromal cells was examined by immunocytochemical method. Relevant extracellular matrix (ECM) proteins and proper cytokines were also assayed for the most suitable condition for expansion of stromal cells. Results: Several cytokines were found to have been produced by CB $CD34^+$ cells as well as bone marrow-derived $CD34^+$ cells. During ex vivo expansion of CB $CD34^+$ cells, stromal cells appeared in the culture by day 4 and expanded over the following 7-10 days before being confluent by day 2 1. These cells expressed surface markers characteristic of cells of endothelial lineage. Furthermore, these stroaml cells also expanded effectively when treated with thrombopoietin+flt-3 ligand+stem cell factor+leukemia inhibitory factor or 0.1% poly-L-lysine-coated wells. Conclusion: Stromal cells were developed during ex vivo expansion of CB $CD34^+$ cells and that this development could be enhanced further by treating the stromal cells with cytokines or ECM.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.6
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• pp.1134-1141
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• 2002

Adhesion of leukocytes to the activated vascular endothelium and their subsequent recruitment/migration into the artery wall are key features in the pathogenesis of atherosclerosis and inflammatory diseases. These features have been mediated by cell adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1) and in tracellular cell adhesion molecule-1 (ICAM-1). This study examined whether flavonoids inhibit the pro-inflammatory cytokine TNF-$\alpha$-induced monocyte adhesion via a modulation of the protein expression of VCAM-1 and ICAM-1 of human umbilical vein endothelial cells (HUVECs). TNF-$\alpha$ markedly increased the adhesion of THP-1 monocytes to endothelial cells and induced the expression of VCAM-1, ICAM-1 and E-selectin proteins in HUVECs. Micromolar concentrations of the flavones luteolin and apigenin and the flavonol quercetin near completely blocked the monocyte adhesion to the activated endothelial cells and the induction of these adhesion molecules. However, equimicromolar catechins of (-)epigallocatechin gallate and (+)catechin, the flavonol myr- icetin and the flavanones of naringin and hesperidin had no effect on TNF-$\alpha$-activated monocyte adhesion. (-)Epigallocatechin gallate, (+) catechin, and naringin did not attenuate the TNF-$\alpha$ induction of these adhesion molecules. Furthermore, culture with luteolin and apigenin strongly blocked the expression of TNF-$\alpha$-induced VCAM-1 mRNA and modestly attenuated ICAM-1 mRNA. Quercetin modestly decreased the TNF-$\alpha$-activated VCAM-1 and ICAM-1 mRNAs. These results demonstrate that flavonoids classified as flavones and flavonols may inhibit monocyte adhesion to the TNF-$\alpha$-activated endothelium, most likely due to a blockade of expression of functional adhesion molecules down-regulated at the transcriptional level, indicating a definite linkage between the chemical structure of flavonoids and the expression of cell adhesion molecules. Furthermore, the antiathero-genic feature of flavonoids appears to be independent of their antioxidant activity.

• Journal of Life Science
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• v.30 no.4
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• pp.343-351
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• 2020

Sorbus commixta Hedl. has traditionally been used as a remedy for cough, asthma, and other bronchial disorders. In this study, three major triterpenoids-lupeol, β-sitosterol, and ursolic acid and a coumarin, scopoletin, were isolated from a CHCl₃-soluble fragment of the bark of S. commixta. Their structures were identified by spectroscopic analyses, including mass spectrometry (MS), 1D-, and 2D- nuclear magnetic resonance spectroscopy (NMR), as well as by comparing the data with data reported in the literature. Scopoletin was isolated from this plant for the first time. It is a nutraceutical compound contained in many plants that has been reported to exert diverse biological activities, including anti-inflammatory effects. This study examined the inhibitory effect of scopoletin on TNF-α-induced vascular endothelial inflammation. Unlike the marginal impact of other compounds against low-density lipoprotein (LDL) oxidation and vascular endothelial inflammation, scopoletin showed remarkable activity on LDL oxidation (IC₅₀ = 10.2 μM) and exerted vascular anti-inflammatory effects in EA.hy926 human endothelial cells activated by TNF-α. It suppressed the expression of adhesion molecules, such as ICAM-1, VCAM-1, and E-selectin, and blocked the adhesion between THP-1 monocytes and EA. hy926 endothelial cells. It also inhibited TNF-α-induced NF-κB translocation from the cytosol to the nucleus. Moreover, IκBα phosphorylation, which was increased by TNF-α treatment, was reduced after treatment with scopoletin. Thus, scopoletin inhibited TNF-α-induced vascular inflammation in endothelial cells by suppressing the NF-κB signaling pathway. These results demonstrate that owing to its anti-inflammatory activity in the vascular endothelium, scopoletin has the potential to inhibit atherosclerosis development.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.90-98
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• 1998

Background : The CD4+ T-helper cells comprise functionally distinct subsets of Th1 and Th2 cells that are distinguished on the basis of differential cytokines production Th1 cells secrete interferon-$\gamma$, lymphotoxin, interleukin-2. Th2 cells produce interleukin-4, interleukin-5, interleukin-10. A previous study shown that Th2 cells and their cytokines increased in patients with atopic asthma. We compared cytokines(IL-4, IFN-$\gamma$) activity and subpopulation of T-lymphocytes in peripheral blood from atopic asthmatics versus non-asthmatics. Method: Fifteen patients with atopic asthma(nine men, six women), twelve patients with chronic bronchitis(six men, six women), five healthy persons(three men, two women) were studied. Activity of IL-4, IFN-$\gamma$ and T-cell subpopulation in peripheral blood were estimated. Results: Patients had a median age of 55yr. The mean activity of IL-4 of asthmatics was significantly increased(control $0.75{\pm}1.1pmol/L$, atopic asthmatics $3.50{\pm}0.75pmol/L$, chronic bronchitis $2.01{\pm}1.2pmol/L$), but IFN-$\gamma$ was not significantly increased. In the T lymphocyte sunsets the percent of CD62L+ T-lymphoeytes of asthmatics was not significantly increased (control $16.7{\pm}16.4%$, atopic asthmatics $24.8{\pm}23.6%$, chronic bronchitis $17.0{\pm}16.9%$). Conclusion: In this study elevated production of IL-4 was observed in atopic asthmatics. CD62L+T-lymphoeytes was not increased in atopic asthma.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.5
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• pp.724-731
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• 2012

This study was designed to elucidate whether combination with Korean red ginseng and Morus alba L. (MPM), traditional treatment for diabetes, ameliorates on high fructose-induced steatohepatitis and vascular inflammation. Animals were divided into four groups; Control receiving tap water, fructose-fed, rosiglitazone-treated fructose-fed rats, and MPM-treated fructose-fed rats both receiving supplemented with 60% fructose (n=10). The MPM or rosiglitazone groups initially received a high-fructose diet alone for 8 weeks, with supplementation with MPM or rosiglitazone, peroxisome proliferators-activated receptor gamma ($PPAR{\gamma}$) agonist, occurring during the final 6 weeks. Treatment with MPM significantly prevented the increase in c-reactive protein (CRP) levels in the high fructose group. MPM suppressed high fructose diet-induced vascular inflammation marker expression such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. MPM also reduced intima/media thickness of thoracic aorta. Histologic observation and oil red O staining demonstrated hepatic tissue damage and lipid accumulation were severe in high fructose group. Treatment with MPM ameliorated hepatic tissue morphology with minimized steatosis. In addition, MPM attenuated hepatitis by inhibition of monocyte chemoattractant protein-1 (MCP-1) expression. MPM-fed group showed lower serum GOT and GPT levels comparing with high fructose group. MPM and rosiglitazone (positive control) significantly decreased the size of epididymal adipocytes. Taken together, the administration of MPM inhibited high fructose-induced steatohepatitis and vascular inflammation. These results suggested that MPM is useful in the prevention or treatment of metabolic syndrome-related disorders such as fatty acid metabolism and vascular homeostasis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.5
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• pp.1337-1345
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• 2006

Hypercholesterolemia is a pivotal pathogenic factor for the development and maintenance of atherosclerosis. The present study was designed to evaluate whether the methanol extract of Sorbus commixta cortex (MSC) restores vascular dysfunction in association with the aortic expressions of proinflarnmatory and adhesion molecules in high cholesterol (HC) diet-rats. Chronic treatment with low (100 mg/kg/day) or high doses (200 mg/kg/day) of MSC lowered the increase in plasma levels of triglyceride (TG) and low-density lipoprotein (LDL) cholesterol induced by a cholesterol-enriched diet without affecting on the plasma level of high density lipoprotein (HDL)-cholesterol. Vascular tone attenuated in the HC-diet rats was restored by administration with MSC. Treatment with MSC also suppressed the HC-induced increase in the monocyte chemoattractant protein-1 (MCP-1) and nuclear factor-$_K$B (NF-$_K$B) p65 expressions as well as expressions levels of adhesion molecules including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (ICAM-1), and E-selectin in aorta. The present study also showed that MSC inhibited the HC-mediated induction of ET-1 and ACE expression. In histopathological examination, aortic segments in the HC-diet rat revealed thickening intima and media, which were blocked by administration with MSC. Taken together, MSC could suppress the development of atherosclerosis in the HC-diet rat model through the inhibition of the aortic expression levels of pro-inflammatory and adhesion molecules.

• Journal of Life Science
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• v.23 no.2
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• pp.311-318
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• 2013

Schisandra chinensis containing a variety of pharmacologically active lignans has been traditionally used in oriental medicine. In this study, anti-inflammatory compounds were screened from the hexane extracts of S. chinensis by activity-guided fractionation. First, we investigated the regulatory effects on the expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) with 38 fractions from the hexane extracts of S. chinensis in human umbilical vein endothelial cells (HUVECs). As a result, SCKH1 among the 38 fractions from the hexane extract of S. chinensis was selected for further analysis based on its unique regulatory effect on cell adhesion molecules, especially on VCAM-1, in LPS-stimulated HUVECs. The subsequent activity-guided fractionation of SCKH1 resulted in the purification of SCKH1PAIBPB, which was found to suppress the expression of VCAM-1, MCP-1, IL-6 and IL-8 in HUVECs stimulated with LPS, and to inhibit the adhesive capacity between HUVECs and monocytes. Taken together, our data indicate that SCKH1PAIBPB can be proposed as an effective anti-inflammatory compound that may have a potential therapeutic use for the prevention and treatment of various inflammatory diseases as well as ischemic vascular diseases.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.308-322
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• 1996

Background : Neutrophils are considered to play critical roles in the development of acute respiratory distress syndrome. Histamine, which is distributed abundantly in lung tissue, increases the rolling of neutrophills via increase of P-selectin expression on the surface of endothelial cells and is known to have some interrelationships with IL-1, IL-8 and TNF-$\alpha$. We studied to investigate the effect of the histamine on the acute lung injury of the rats induced by intratracheal insufflation of TNF-$\alpha$ which has less potency to cause lung injury compared to IL-1 in rats. Methods : We intratracheally instilled saline or TNF(R&D, 500ng), IL-1(R&D, 50ng)or histamine of varius dose(1.1, 11 and $55\;{\mu}g/kg$) with and without TNF separately in Sprague-Dawley rats weighing 270-370 grams. We also intratracheally treated IL-1(50ng) along with histamine($55\;{\mu}g/kg$). In cases, there were synergistic effects induced by histamine on the parameters of TNF-induced acute lung injury, antihistamines(Sigma, mepyramine as a $H_1$ receptor blockade and ranitidine as a $H_2$ receptor blockade, 10 mg/kg in each)were co-administered intravenously to the rats treated TNF along with histamine($1.1\;{\mu}g/kg$) intratraeheally. Then after 5 h we measured lung lavage neutrophil numbers, lavage cytokine-induced neutrophil chemoattractants(CINC), lung myeloperoxidase activity(MPO) and lung leak. We also intratracheally insufflated TNF with/without histamine($11\;{\mu}g/kg$), then after 24 h measured lung leak in rats. Statistical analyses were done by Kruskal-Wallis nonparametric ANOVA test with Dunn's multiple comparison test or by Mann-Whitney U test. Results : We found that rats given TNF, histamine alone(11 and $55\;{\mu}g/kg$), and TNF with histamine(l.1, 11, and $55\;{\mu}g/kg$) intratracheally had increased (p<0.05) lung MPO activity compared with saline-treated control rats. TNF with histamine $11\;{\mu}g/kg$ had increased MPO activity (P=0.0251) compared with TNF-treated rats. TNF and TNF with histamine(1.1, 11, and $55\;{\mu}g/kg$) intratracheally had all increased (p<0.05) lung leak, lavage neutophil numbers and lavage CINC activities compared with saline. TNF with histamine $1.1\;{\mu}g/kg$ had increased (p=0.0367) lavage neutrophil numbers compared with TNF treated rats. But there were no additive effect of histamine with TNF compared with TNF alone in acute lung leak on 5 h and 24 h in rats. Treatment of rats with the $H_1$ and $H_2$ antagonists resulted in inhibitions of lavage neutrophil accumulations and lavage CINC activity elevations elicited by co-treated histamine in TNF-induced acute lung injury intratracheally in rats. We also found that rats given IL-1 along with histamine intratracheally did not have increase in lung leak compared with IL-1 treated rats. Conclusion : Histamine administered intratracheally did not have synergistic effects on TNF-induced acute lung leak inspite of additive effects on increase in MPO activity and lavage neutrophil numbers in rats. These observations suggest that instilling histamine intratracheally would not play synergistic roles in neutrophil-mediated acute lung injury in rats.