• International Journal of Oral Biology
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• 제37권3호
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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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• 제16권5호
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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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• 제48권9호
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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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• 제17권1호
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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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• 제41권1호
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• pp.11-19
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• 1994

연구배경 : 결핵균은 facultative intracellular pathogen으로 대식세포에서 생존 번식할 수 있으며, 결핵균이 체내에서 제거되려면 대식세포와 T 임파구에 의한 효과적인 세포매개성 면역반응이 필요하다. 폐포대식세포에 의한 결핵균 살균은 크게 산소의존성 과정과 산소비의존성 과정으로 구분되는데 산소의존성과정은 NADPH oxidase에 의해 산소가 환원반응으로 과산화음이온을 생성하는 과정으로 시작된다. 저자들은 폐결핵환자의 경우 폐포대식세포의 산소유리기 생성의 이상으로 결핵균이 세포내 오래 생존 번식할 것으로 추정하여 폐결핵환자와 대조군에서 폐포대식세포와 말초혈액 단구세포를 분리하여 분비되는 과산화음이온의 양을 비교하여 보았다. 방법 : 대조군과 폐결핵환자에서 폐포대식세포와 말초혈액내 단구세포를 분리하여 기저상태 및 PMA로 자극한 후 분비되는 과산화음이온의 양을 ferricytochrome-C를 환원시켜 나타나는 발색반응을 이용하여 측정하였고, 단구세포의 경우 결핵환자의 혈청에 의해 어떤 변화를 보이는지 관찰하였다. 결과 : 1) 폐포대식세포에서 분비하는 과산화음이온은 폐결핵환자군와 대조군 사이에 차이가 없었고, PMA로 자극을 했을 때도 두군 사이에 차이가 없이 모두 유의한 증가를 보였다. 2) 말초혈액 단구세포에서 분비하는 과산화음이온은 폐결핵환자군과 대조군 사이에 차이가 없었지만, PMA로 자극을 했을 때 두군에서 모두 유의한 증가를 보였고 폐결핵환자군이 대조군에 비해 높았다. 한편 결핵환자 혈청으로 폐결핵환자군과 대조군의 말초혈액 단구세포를 자극했을 때도 두군에서 모두 유의하게 증가되었다. 결론 : 폐포대식세포와 말초혈액 단구세포에서 분비하는 과산화음이온의 양은 정상인과 폐결핵환자에서 차이가 없었다. 따라서 폐포대식세포에서의 과산화음이온 분비가 부족하여 결핵균이 폐포대식세포내에서 장기간 생존하는 것으로 생각되지 않으며, 오히려 결핵환자의 혈청내에는 말초혈액 단핵구의 과산화음이온 분비를 자극하는 물질이 있을 것으로 생각되나, 정상인 혈청이 과산화음이온 생성에 미치는 효과에 대한 비교 연구가 필요할 것으로 사료된다.

• The Korean Journal of Physiology and Pharmacology
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• 제17권2호
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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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• 제5권5호
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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.

• 대한한의학방제학회지
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• 제20권1호
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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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• 제29권4호
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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.

• 한국식품영양과학회지
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• 제40권5호
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• pp.635-641
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• 2011

본 연구는 TNF-${\alpha}$로 자극된 HUVEC에서 녹차씨껍질 EtOAC 추출물이 초기 동맥경화 과정에 중요한 역할을 하는 염증매개인자와 세포부착물질에 미치는 영향을 분석하였다. 녹차씨껍질 EtOAC 추출물의 NO 생성능은 TNF-${\alpha}$만을 처리한 control군에 비해 증가시키는 것을 알 수 있었다. $100{\mu}g$/mL 농도에서는 녹차씨껍질 EtOAC 추출물은 세포독성을 보이지 않았으며 염증매개인자인 TNF-${\alpha}$ 수준 및 세포부착물질인 VCAM-1과 MCP-1의 생성을 억제하였다. 뿐만아니라, 녹차씨껍질 EtOAC 추출물은 총 항산화능은 증가되는 경향을 보였다. 이상의 결과에서, 녹차씨껍질 EtOAC 추출물은 HUVEC에서 TNF-${\alpha}$로 인한 총 항산화능의 수준을 향상시켜 염증생성인자인 TNF-${\alpha}$ 수준 및 세포부착물질인 VCAM-1과 MCP-1의 생성을 억제하여 동맥경화 초기반응을 억제하는데 기여할 것으로 사료된다.