• 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.

• 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.

• BMB Reports
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• v.48 no.9
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• pp.519-524
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• 2015

Vascular inflammatory process has been suggested to play a key role in initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, in this study, we attempted to determine whether three structurally related polyphenols found in the Chinese herb Huang Qui, namely baicalin, baicalein, and wogonin, can suppress vascular inflammatory processes induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Data showed that HG induced markedly increased vascular permeability, monocyte adhesion, expressions of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS) and activation of nuclear factor (NF)-κB. Remarkably, all of the above mentioned vascular inflammatory effects of HG were attenuated by pretreatment with baicalin, baicalein, and wogonin. Vascular inflammatory responses induced by HG are critical events underlying development of various diabetic complications, therefore, our results suggest that baicalin, baicalein, and wogonin may have significant therapeutic benefits against diabetic complications and atherosclerosis. [BMB Reports 2015; 48(9): 519-524]

• Food Science and Biotechnology
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• v.17 no.1
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• pp.38-45
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• 2008

Antioxidant and anti-rheumatoid activities of Cirsium japonicum leaf extract (CJLE) were investigated in this study. CJLE had similar DPPH radical scavenging activity and reducing power to ascorbic acid and several flavonoids. Rheumatoid arthritis (RA) is a chronic inflammatory tissue-destructive disease, partly related with functions of hyaluronidases (HAases) and collgenases. CJLE ($1,000\;{\mu}g/mL$) had approximately 60.7 and 31.9% inhibition of HAase and collagenase activity, respectively. Also, CJLE inhibited lipopolysaccharide (LPS)-induced nitrite production in a dose-dependent manner, and CJLE ($1,000\;{\mu}g/mL$) suppressed approximately 70% of LPS-induced nitrite production effectively in RAW 264.7 macrophage cells. CJLE had inhibitory effects on the adherence of monocytic THP-1 to human umbilical vein endothelial cell (HUVEC) monolayers to the basal level. Inhibitory effect of CJLE on the adhesion was caused by suppression of tumor necrosis factor-a-upregulated expression of vascular cellular adhesion molecule-1 (VCAM-1) and E-selectin. We expect that CJLE may alleviate the inflammatory process in rheumatoid synovium, and these findings will raise the possibility of the usage of C. japonicum as a traditional pharmaceutical of anti-rheumatoid arthritis.

• Tuberculosis and Respiratory Diseases
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• v.41 no.1
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• pp.11-19
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• 1994

Background: Mycobacterium tuberculosis is a facultative intracellular pathogen which persists and multiplies within macrophage. Competent cell mediated immunity by cooperation of both T lymphocyte and macrophage of the host is required to kill the Mycobacterium tuberculosis. But a precise understanding of the pathogenesis of tuberculosis infection in pulmonary alveolar macrophage has not been achived. Research on the macrophage's basic microbicidal mechanism has elucidated the importance of oxygen-dependent or oxygen-independent components. Oxygen dependent processing begins with the reduction of oxygen by NADPH oxidase and generation of superoxide. In this study, the oxidative metabolic status of blood monocyte and pulmonary alveolar macrophage in patients with active pulmonary tuberculosis was accessed and compared with that of healthy control subjects to know whether there was a basic difference in superoxide generation by mononuclear cells between two groups. Methods: Pulmonary alveolar macrophage was purified after performing BAL(bronchoalveolar lavage) through the bronchi of infected lesion by plastic adhesion method. Blood monocyte was purified by Ficoll-Hypaque method. Superoxide generation by blood monocyte and pulmonary alveolar macrophage was measured by ferricytochrome-C reduction method after either stimulated with PMA(phorbol myristate acerate) or non-stimulated states. We also measured the effect of pulmonary tuberculosis patient's serum on superoxide generation by monocyte. Results: 1) Generation of superoxide by alveolar macrophage obtained from patients with pulmonary tuberculosis was little higher than those of controls, and PMA enhanced the generation of 2) Generation of superoxide by blood monocyte obtained from patients with pulmonary tuberculosis was little higher than those of control(p>0.05), and PMA more enhanced the generation of superoxide in patientswith pulmonary tuberculosis than those in controls(p<0.02). 3) Patient's serum enhanced the generation of superoxide by blood monocyte obtained from patients with pulmonary tuberculosis and controls, but not in the case of PMA stimulated blood monocyte. Conclusion: The present study suggest that the phenomenon of M.tuberculosis escape the microbicidal action of macrophage was not result of suppressed superoxide generation by blood monocyte and pulmonary alveolar macrophage, rather there might be a factor to stimulate the generation of superoxide by blood monocyte in pulmonary tuberculosis patient serum, but the comparision with effect of control's serum on superoxide generation needs further elucidation.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.2
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• pp.133-137
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• 2013

Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea. In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC). LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-${\kappa}B$) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaB${\alpha}$ ($I{\kappa}B{\alpha}$) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of $I{\kappa}B{\alpha}$ expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease.

• Nutrition Research and Practice
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• v.5 no.5
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• pp.381-388
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• 2011

We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-${\alpha}$-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-${\alpha}$ exposure significantly increased expression of monocyte chemoattractant protein (MCP)-l, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-l and VCAM-l production in a dose-dependent manner, whereas CAM expression was not significantly lowered by genistein treatment. However, daidzein slightly decreased MCP-l production. The effects of genistein and daidzein on MCP-l secretion coincided with mRNA expression. Pre-treatment with either genistein or daidzein elevated eNOS expression and nitric oxide production disturbed by TNF-${\alpha}$ exposure. A low concentration of isoflavones significantly inhibited nuclear factor (NF)${\kappa}$B activation, whereas a high dose slightly ameliorated these inhibitive effects. These results suggest that genistein had a stronger effect on MCP-l and eNOS expression than that of daidzein. Additionally, NF${\kappa}$B transactivation might be partially related to the down-regulation of these mRNAs in TNF-${\alpha}$-stimulated HUVECs.

• Herbal Formula Science
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• v.20 no.1
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• pp.1-11
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• 2012

Objectives : This experimental study was designed to investigate the inhibitory effects of combination with Korean red ginseng and Gastrodia rhizoma on vascular dysfunction in high-fat/cholesterol diet-induced hyperlipidemia. Methods : Sprague-Dawley rats were fed with 7.5% cocoa butter and 1.25% cholesterol for 10 weeks, with Panax ginseng (PG), and mixtures of Panax ginseng and Gastrodia rhizoma (PGM), respectively. Results : Chronic treatment with PG and PGM significantly decreased body weight. The aortic expression of cell adhesion molecules such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin were markedly increased in hyperlipidemia rats. Interestingly, PGM significantly decreased cell adhesion molecules expression. However, there was no significant decrease in PG group. In addition, PG and PGM group inhibited high-fat/cholesterol diet-induced cytokine such as monocyte chemoattractant protein (MCP-1) mRNA expression. Furthermore, PG and PGM group significantly decreased c-reactive protein protein (CRP) level. Especially, PGM significantly accentuated the decrease of MCP-1 mRNA expression and CRP level. Conclusions : the present study provides an evidence that combination with Panax ginseng and Gastrodia rhizoma enhances anti-vascular protective effects through suppression of vascular inflammation in hyperlipidemic rats.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.5
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• pp.635-641
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• 2011

Anti-atherogenic effects in tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-stimulated human umbilical vein endothelial cells (HUVEC) are involved with suppressed oxidative stress, cell adhesion molecules, and pro-inflammatory factors. The aim of this study was to determine whether green tea seed coat ethyl acetate fraction (GTSCE) could modulate cell adhesion molecules and inflammatory mediators in HUVEC stimulated with TNF-${\alpha}$. Nitric oxide (NO) production was significantly increased in TNF-${\alpha}$-stimulated HUVEC compared to TNF-${\alpha}$ only treated cells. The NO that is produced by endothelial nitric oxide synthase dilates blood vessels and has protective effects against platelet and leucocyte adhesion. GTSCE at 25, 50, 75, and $100\;{\mu}g$/mL significantly (p<0.05) reduced TNF-${\alpha}$ production. GTSCE significantly (p<0.05) inhibited soluble vascular cell adhesion molecule-1 level, in a dose-dependent manner. Monocyte chemoattractant protein-1 level was also significantly (p<0.05) inhibited by GTSCE treatment at $75\;{\mu}g$/mL compared to the TNF-${\alpha}$-only treated group. Total antioxidant capacity by GTSCE was significantly (p<0.05) enhanced compared to the TNF-${\alpha}$-only treated group. These results suggest that GTSCE can inhibit the production of cell adhesion molecules and inflammatory mediators and could be used as a candidate bioactive material to prevent the development of atherosclerosis.