• 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.

• Tuberculosis and Respiratory Diseases
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• v.56 no.4
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• pp.364-373
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• 2004

Background : Obstructive sleep apnea is a contributory factor of hypertension, arrhythmia, ischemic heart disease and other cardiovascular diseases. However, the pathophysiology underlying this relationship is unclear. Recent reports have shown that the soluble intercellular adhesion molecule-1(sICAM-1) and vascular endothelial growth factor(VEGF) are involved in the initiation and progression of atherosclerosis, and some reports state that increased levels of these cytokines are found in patients with obstructive sleep apnea. In this study, the levels of sICAM-1 and VEGF were measured in patients with obstructive sleep apnea in order to determine if obstructive sleep apnea is involved in the pathophysiology of cardiovascular diseases. Methods : Thirty-seven patients were chosen amongst a population who visited the Sleep Disorders Clinic of St. Paul's Hospital in Seoul, Korea for a diagnosis of obstructive sleep apnea and who had subsequently undergone an overnight polysomnography at the clinic. The sera from these patients were retrieved after an overnight polysomnography session and the samples were kept at $-70^{\circ}C$. The cytokine levels were determined with ELISA and the relationships between the serum levels of sICAM-1 and VEGF along with polysomnography parameters were analyzed. Results : No statistically significant correlation was observed between the sICAM-1 levels and the apnea-hypopnea index(r=0.27, P>0.05). Positive correlations were found between the apnea-hypopnea index and serum VEGF levels (r=0.50, P<0.01), the apnea index and the serum sICAM-1 levels (r=0.31, P<0.01), and the apnea index and the serum VEGF levels (r=0.45, P<0.01). Conclusions : Obstructive apnea or hypopnea leads to an increase in the sICAM-1 and VEGF levels. Such an increase in the cytokine levels most likely leads to the higher incidence of cardiovascular diseases observed in patients with obstructive sleep apnea.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1579-1583
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• 2013

Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin superfamily, its main function being to participate in recognition and adhesion between cells. ICAM-1 is considered closely related to occurrence, development, metastasis and invasion process of hepatocellular carcinoma (HCC). A variety of inflammatory cytokines and stimulus affect its expression through the nuclear factor-kappa B (NF-${\kappa}B$) signal transduction pathway. In the initial stage of inflammation, hepatocirrhosis and tumor development, ICAM-1 is expressed differently, and has varied effects on different cells to promote occurrence of malignancy and metastasis. ICAM-1 has diagnostic significance for AFP-negative or suspected HCC, and may be a prognositic significance. It is thus widely used in studies as a biomarker which reflects cancer cells metastasis as well as curative effect of drugs. Many new treatments of HCC may be based on the effects of ICAM-1 on different levels of function.

• IMMUNE NETWORK
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• v.2 no.1
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• pp.6-11
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• 2002

Background: Inflammation is a frequent reaction following therapeutic irradiation. Since the upregulation of adhesion molecules on endothelial cell surface is known to be associated with inflammation, the expression of adhesion molecules is an important therapeutic target. Methods: Treatment of human umbilical endothelial cells (HUVECs) with ${\gamma}$-irradiation (${\gamma}IR$) induces the expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Changes in the expression of these proteins on ${\gamma}$-irradiated HUVECs which had been treated previously with allicin were measured by ELISA. Results: In the present study, we demonstrate that allicin inhibits the ${\gamma}IR$ induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose-dependent manner. Allicin was also found to inhibit the ${\gamma}IR$ induced production of nitric oxide (NO). Conclusion: These data suggest that allicin has a therapeutic potential for the treatment of various inflammatory disorders associated with increase numbers of endothelial leukocyte adhesion molecules.

• Animal cells and systems
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• v.5 no.3
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• pp.253-262
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• 2001

Ligand-receptor clustering event is the most important step in leukocyte adhesion and spreading on endothelial cells. Intercellular adhesion molecule-1 (ICAM-1) has been shown to enhance leukocyte adhesion, but the molecular event during the process of adhesion is unclear. To visualize the dynamics of ICAM-1 movement during adhesion, we have engineered stable Chinese hamster ovary cell lines expressing ICAM-1 fused to a green fluorescent protein (IC1_GFP/CHO) and examined them under the fluorescence microscopy. The transfection of IC1_GFP alone in these cells was sufficient to support the adhesion of K562 cells that express $\alpha$L$\beta$2 (LFA-1) integrin stimulated by CBR LFA-1/2 mAb. This phenomenon was mediated by ICAM-1-LFA-1 interactions, as an mAb that specifically inhibits ICAM-1-LFA-1 interaction (RRl/l) completely abolished the adhesion of LFA-1＊ cells to IC1_ GFP/CHO cells. We found that the characteristic of adhesion was followed almost immediately (~10 min) by the rapid accumulation of ICAM-1 on CHO cells at a tight interface between the two cells. Interestingly, ICI_GFP/CHO cells projected plasma membrane and encircled approximately half surface of LFA-1+ cells, as defined by confocal microscopy. This unusual phenomenon was also confirmed on HUVEC after adhesion of LFA-1＊ cells. Neither cytochalasin D nor 2,3-butanedione 2-monoxime an inhibitor of myosin light chain kinase blocked LFA-1-mediated ICAM-1 clustering, indicating that actin cytoskeleton and myosin-dependent contractility are not necessary for ICAM-1 clustering. Taken together, we suggest that leukocyte adhesion to endothelial cells induces specialized form of ICAM-1 clustering that is distinct from immunological synapse mediated by T cell interaction with antigen presenting cells.

• Biomolecules & Therapeutics
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• v.9 no.3
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• pp.156-161
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• 2001

Inflammation is a frequent radiation-induced following therapeutic irradiation. Treatment of human umbilical endothelial cells (HUVEC) with ${\gamma}$-irradiation (${\gamma}$IR) induces the expression of adhesion proteins such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Since the upregulation of these proteins on endothelial cell surface has been known to be associated with inflammation, interfering with the expression of adhesion molecules is an important therapeutic target. In the present study, we demonstrate that bioflavonoid rutin inhibits ${\gamma}$IR induced expression of ICAM-1, VCAM-1, and E-selectin on HUVEC in a dose- and time dependent manner. Rutin also inhibited ${\gamma}$IR induced production of NO. These data suggest that rutin has therapeutic potential for the treatment of various inflammatory disorder associated with an increase of endothelial leukocyte adhesion molecules.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.307.1-307.1
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• 2002

Inflammation is a frequent radiation-induced following therapeutic irradiation. Since the upregulation of adhesion molecules on endothelial cell surface has been known to be associated with inflammation. interfering with the expression of adhesion molecules is an important therapeutic target. We examined the effect of allicin. a major component of garlic. on the induction of intercellular adhesion molecule-1 (lCAM-1) by gamma-irradiation and the mechanisms of its effect in gamma-irradiated human umbilical vein endothelial cells (HUVECs). (omitted)

• Journal of Korean Neurosurgical Society
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• v.29 no.4
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• pp.477-484
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• 2000

Objective : Despite advances in the understanding of tumor biology and the tumor immunology, there has been no effective treatment. The Intercellular adhesion molecule-1(ICAM-1) has been shown to be important in interaction involving cells of the immune system and to be upregulated in a number of cell culture systems by cytokines, including immune interferon($IFN-{\gamma}$) and tumor necrosis $factor-{\alpha}$($TNF-{\alpha}$). ICAM-1 has been identified as one of the ligands for lymphocyte function-associated antigen-1(LFA-1). The effectiveness of various cytokines to ICAM-1 induction on cultured human glioblastoma cell lines and potential efficacy of immunotherapy were studied. Method : Human glioblastoma cell lines, U-251 MG, U-373 MG were trypsinized and suspended at $1{\times}10^5cells/ml$ and grown on 8 well chamber slide, the cells were incubated in 0.3ml medium alone or medium containing $IFN-{\gamma}$(1000U/ml) or $TNF-{\alpha}$(250U/ml) or $IFN-{\gamma}$ plus $TNF-{\alpha}$ for 6, 12, 24, 48 and 72 hours. The coverslip were then removed and stained with a 1/30 dilution of anti-ICAM-1 antibody. Result : Surface antigen expression of ICAM-1 was increased by incubating glioblastoma cell lines with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\gamma}$ and $TNF-{\alpha}$ has induced more ICAM-1 expression on glioblastoma cell lines. Upregulation of ICAM-1 expression in an established glioblastoma cell line was of greater magnitude and more rapid following incubation with $IFN-{\gamma}$ plus $TNF-{\alpha}$. Surface antigen expression of ICAM-1 was increased for up to 48 hours after cytokine treatment on both cell lines(p<0.05). There was no difference on both cell lines(p>0.05). Conclusion : The results of the present study indicate that ICAM-1 expression in glioblastoma cell lines, U-251 MG and U-373 MG, are induced and enhanced after treatment with $IFN-{\gamma}$ and $TNF-{\alpha}$. Combined effect of $IFN-{\alpha}$ and $TNF-{\gamma}$ is stronger and more rapid than $IFN-{\gamma}$ or $TNF-{\alpha}$ alone.

• Journal of Korean Neurosurgical Society
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• v.38 no.1
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• pp.1-11
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• 2005

Objective : The purpose of this study is to evaluate the correlation of the ICAM-l levels in serum and CSF with cerebral vasospasm in early aneurysmal subarachnoid hemorrhage [SAH] patients. Methods : A prospective analysis was performed in thirty consecutive patients who underwent early surgery for intracranial aneurysmal SAH. The serum and CSF were obtained daily through the indwelling arterial lines and intraoperative ventriculostomy, or cisternal drain for 4 consecutive days after surgery. The ICAM-1 levels in serum and CSF samples were measured via quantitative enzyme-linked immunosorbent assay. Results : The mean concentration of serum in aneurysmal SAH patients was 207.89ng/ml compared with 132.25ng/ml in controls. The mean concentration of CSF in aneurysmal SAH patients was 76.39ng/ml compared with 3.96ng/ml in controls. There were no significant differences between serum and CSF ICAM-1 level with regards to clinical characteristics in patients with aneurysmal SAH [P>0.05]. However, CSF ICAM-1 levels increased significantly in patients with vasospasm compared with those without vasospasm [P<0.05]. Conclusion : The major result of this study shows that ICAM-1 is increased in CSF after early aneurysmal SAH and that this increase in ICAM-1 has correlation with cerebral vasospasm. Further study is needed to determine whether ICAM-1 levels may be indicator in the pathogenesis of important events leading to cerebral vasospasm.

• The Journal of Korean Society of Virology
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• v.26 no.1
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• pp.47-58
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• 1996

Histopathological vascular changes in hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus include increased vascular permeability, disseminated intravascular coagulation, thrombocytopenia and changes in coagulation activity. Although vascular endothelial cells of main target organs such as kidney infected with Hantaan virus are not damaged but swelling of endothelial cells, perivascular exudates and infiltration of mononuclear cells and fresh interstitial hemorrhages are common. However, the pathogenesis of cell infiltration and hemorrhages around vascular endothelial cells are not well understood. Some endothelial cell molecules or vascular adhesins that acts as adhesion moleulces for leukocyte are expressed on endothelial cells close to site of inflammation. However, whether the expression of endothelial adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial leukocyte adhesion molecule (ELAM) on vascular endothelial cells are increased by infection with Hantaan virus has not been studied. In this study, the relationship between the expression of VCAM-1, ICAM-1 and ELAM and adhesion of mononuclear cells on endothelial cells of human blood vessels infected with Hantaan virus was investigated. The endothelial cells of umbilical vein was passaged three times in culture medium and the monolayered cells were infected with $10^5\;pfu/ml$ of Hantaan virus grown in Vera E6 cell cultures. The multiplication of virus in cultured endothelial cells was monitored by immunohistochemistry and the expression of adhesion molecules was demonstrated by immunohistochemistry using monoclonal antibodies against VCAM-1, ICAM-1 and ELAM. And in situ hybriditation against ICAM-1 was also performed. The endothelial adhesion molecules, VCAM and ICAM, were expressed after 6 hours postinfection, respectively, and their expressions lasted for 72 hours. Similar expression of VCAM and ICAM appeared on endothelial cells by infection with virus, but the expression of ELAM was not recognized up to 72 hours postinfection. Microscopically, it was noted that many monocuclear cells adhered on endothelial cells infected with viruses. In an electronmicroscopic study, the transendothelial migration of mononuclear cells was observed on monolayered endothelial cells infected with virus. This results suggested that the endothelial adhesion molecules, particulary VCAM and ICAM, might be expressed on endothelial cells by infection with Hantaan virus and these molecules play a key role in the adhesion and extravasation of inflammatory cells around blood vessels.