• Archives of Pharmacal Research
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• v.27 no.10
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• pp.1073-1079
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• 2004

Interactions of the cell adhesion molecules are known to play important roles in mediating inflammation. The proinflammatory cytokine, tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), activates the NF-kB signaling pathway, which induces the expression of various genes, such as intercellular adhesion molecule-1 (ICAM-1). In this study, the effect of vitamin C on the ICAM-1 expression induced by TNF-${\alpha}$ in a human neuroblastoma cell line, SK-N-SH was investigated. Treatment with vitamin C resulted in the downregulation of the TNF-${\alpha}$-induced surface expression and ICAM-1 mRNA levels in a concentration-dependent manner. Moreover, a gel shift analysis indicated that vitamin C dose-dependently inhibited the NF-kB activation and IkB${\alpha}$ degradation induced by TNF-${\alpha}$. Taken together, these results suggest that vitamin C downregulates TNF-${\alpha}$- induced ICAM-1 expression via the inhibition of NF-kB activation.

• Environmental Mutagens and Carcinogens
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• v.25 no.4
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• pp.143-149
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• 2005

The identification of COX-2 (cyclooxygenase-2) has led to potential novel insights on disease pathogenesis (atherosclerosis, cancer, Alzheimer's disease) and the regulation of normal organ function. The present in vivo study with estrogen or soy-isoflavones has provided evidence for the association between COX-2 and ICAM-1 (Intercellular adhersion molecule-1). In the system of mature female rats, soy-isoflavones exerted more pronounced effect on ICAM-1 inhibitory and COX-2 stimulatory effect than estrogen. In the system of ovariectomized estrogen deficient rats, the down-regulatory properties of soy-isoflavones on ICAM-1 was less evident, whereas estrogen exerted the inhibitory activity. These results demonstrate that COX-2 limits adhersion molecule expression on rat aorta cells and suggest that COX-2 may play a protective role in cardiovascular system in mature female rats. Soy-isoflavones appear to have beneficial effect on vascular systems through modulation of ICAM-1 and COX-2, and these molecules appeared to be closely associated.

• Journal of Life Science
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• v.17 no.3 s.83
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• pp.396-401
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• 2007

This research investigated whether exposure of diesel exhaust particulate (DEP) and particulate metter (PM) effect on intercellular. adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression in asthma-induced Balb/c and IL-10 knock out (KO) mouse. Mouse was sensitized with intraperitoneal injection with ovalbumin, followed by challenges with intranasal ovalbumin. After induction of asthma mouse placed in the inhalation chamber and exposed to DEP and PM (10 $mg/m^3$). The evidences of pulmonary inflammation were assessed by immunohistochemical stain and westen blot against ICAM-1 and VCAM-1 in the lung tissue. In the immunohistochemical stain, positive reactions for ICAM-1 and VCAM-1 were much stronger in asthma-induced groups and asthma-induced group with DEP or PM than control groups. Although mild positive reactions were appeared in asthma-induced IL-10 KO mice groups, positive reactions were very strong in the asthma-induced group with DEP or PM. In Western blot, expression of VCAM-1 was increased in asthma-induced group with DEP or PM than asthma-induced groups. In the IL-10 KO mouse, ICAM-1 and VCAM-1 expression were increased in asthma-induced group with DEP or PM than asthma-induced groups. DEP and PM exposure have additive effects on the aggravation of inflammatory signs in the asthma-induced murine model. These results suggest that inhalation of DEP and PM in asthmatic patients may aggravate clinical symptoms.

• Molecules and Cells
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• v.38 no.9
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• pp.821-828
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• 2015

Monocytes are the major inflammatory cells that infiltrate most solid tumors in humans. The interaction of tumor cells with infiltrating monocytes and their adhesion to these monocytes play a significant role in altering the tumor to become more aggressive. Recently, exposure to lipopolysaccharide (LPS) was suggested to promote cancer cell adhesion to monocytes; however, little is known about the details of the signaling mechanism involved in this process. In this study, we found that LPS up-regulates ICAM-1 expression in MDA-MB-231 breast cancer cells, which facilitates their adhesion to THP-1 monocytes. In addition, we analyzed the signaling mechanism underlying the up-regulation of ICAM-1 and found that the siRNA-mediated depletion of BLT2 markedly suppressed the LPS-induced expression of ICAM-1 in MDA-MB-231 cells and the subsequent adhesion of these cells to THP-1 monocytes. Moreover, we demonstrated that myeloid differentiation primary response gene 88 (MyD88) lies downstream of LPS/TLR4 and upstream of BLT2 and that this 'MyD88-BLT2' cascade mediates ERK activation and subsequent ICAM-1 expression, which is critical for the adhesion of MDA-MB-231 cells to THP-1 monocytes. Taken together, our results demonstrate for the first time that LPS up-regulates ICAM-1 expression in breast cancer cells via a MyD88-BLT2-ERK-linked signaling cascade, leading to the increased adhesion of breast cancer cells to monocytes.

• BMB Reports
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• v.39 no.5
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• pp.618-625
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• 2006

The infiltration of both monocyte and activated T cells in the skin is one of critical steps in the development of UVB-induced inflammation. Upregulation of adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) on the surface of keratinocytes plays an important role in this process. In this study, we examined the molecular mechanism responsible for UVB-induced expression of ICAM-1 and subsequent monocyte adhesion by keratinocyte. We observed that (1) UVB induced protein and mRNA expression of ICAM-1 in a dose- and time-dependent manner in human keratinocyte cell HaCaT; (2) UVB induced the translocation of NF-kappaB and inhibition of NF-kappaB by NF-kappaB inhibitors suppressed UVB-induced mRNA and protein expression of ICAM-1; (3) UVB increased the intracellular level of reactive oxygen species (ROS) by HaCaT cells; (4) UVB-induced increase of intracellular ROS level was suppressed by pre-treatment with diphenyl iodonium (DPI) and N-acetyl cysteine (NAC); and (5) inhibition of UVB-induced ROS production by DPI or NAC suppressed UVB-mediated translocation of NF-kappaB, expression of ICAM-1 and subsequent monocyte adhesion in HaCaT cells. These results suggest that UVB-induced ROS is involved in the translocation of NF-kappaB which is responsible for expression of ICAM-1 and subsequent increased monocyte adhesion in human keratinocyte.

• BMB Reports
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• v.46 no.8
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• pp.410-415
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• 2013

Adhesion molecules such as ICAM-1 are important in the infiltration of leukocytes into the site of inflammation. In this study, we investigated the inhibitory effects of curcumin on ICAM-1 expression and monocyte adhesiveness as well as its underlying action mechanism in the TNF-${\alpha}$-stimulated keratinocytes. Curcumin induced expression of heme oxygenase-1 (HO-1) in the human keratinocyte cell line HaCaT. In addition, curcumin induced Nrf2 activation in dose- and time-dependent manners in the HaCaT cells. Curcumin suppressed TNF-${\alpha}$-induced ICAM-1 expression and subsequent monocyte adhesion, which were reversed by the addition of tin protoporphyrin IX (SnPP), a specific inhibitor of HO-1, or HO-1 knockdown using siRNA. Furthermore, Nrf2 knockdown using siRNA reversed the inhibitory effect of curcumin on the TNF-${\alpha}$-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that curcumin may exert its anti-inflammatory activity by suppressing the TNF-${\alpha}$-induced ICAM-1 expression and subsequent monocyte adhesion via expression of HO-1 in the keratinocytes.

• 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.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.342-351
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• 2021

Liver colonization is initiated through the interplay between tumor cells and adhesion molecules present in liver sinusoidal endothelial cells (LSECs). This crosstalk stimulates tumor COX-2 upregulation and PGE2 secretion. To elucidate the role of the LSEC intercellular adhesion molecule-1 (ICAM-1) in the prometastatic response exerted by tumor and stromal COX-2, we utilized celecoxib (CLX) as a COX-2 inhibitory agent. We analyzed the in vitro proliferative and secretory responses of murine C26 colorectal cancer (CRC) cells to soluble ICAM-1 (sICAM-1), cultured alone or with LSECs, and their effect on LSEC and hepatic stellate cell (HSC) migration and in vivo liver metastasis. CLX reduced sICAM-1-stimulated COX-2 activation and PGE2 secretion in C26 cells cultured alone or cocultured with LSECs. Moreover, CLX abrogated sICAM-1-induced C26 cell proliferation and C26 secretion of promigratory factors for LSECs and HSCs. Interestingly, CLX reduced the protumoral response of HSC, reducing their migratory potential when stimulated with C26 secretomes and impairing their secretion of chemotactic factors for LSECs and C26 cells and proliferative factors for C26 cells. In vivo, CLX abrogated the prometastatic ability of sICAM-1-activated C26 cells while reducing liver metastasis. COX-2 inhibition blocked the creation of a favorable tumor microenvironment (TME) by hindering the intratumoral recruitment of activated HSCs and macrophages in addition to the accumulation of fibrillar collagen. These results point to COX-2 being a key modulator of processes initiated by host ICAM-1 during tumor cell/LSEC/HSC crosstalk, leading to the creation of a prometastatic TME in the liver.

• Tuberculosis and Respiratory Diseases
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• v.43 no.1
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• pp.75-87
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• 1996

Background: Lung cancer is the second most frequent malignancy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1(sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. Subjects: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. Result: Clinically significant radiation pneumonitis developed in 7 patients. After RT, total cell count in BAL was significantly increased from $(20.2{\pm}10.2){\times}10^6\;cells/ml$ to $(35.3{\pm}21.6){\times}10^6\;cells/ml$ (p=0.0344) and %lymphocyte was also increased from $5.3{\pm}4.2%$ to $39.6{\pm}23.4%$ (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: $378{\pm}148$, $411{\pm}150\;ng/ml$, BALF: $20.2{\pm}12.2$, $45.1{\pm}34.8\;ng/ml$, respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: $505{\pm}164$ vs $345{\pm}102\;ng/ml$, p=0.0253, BALF: $67.9{\pm}36.3$ vs $25.2{\pm}17.9\;ng/ml$, p=0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from $1.28{\pm}0.479$ to $1.63{\pm}0.539$, p=0.0605), but it was significantly high in patients with pneumonitis ($2.10{\pm}0.390$) compared to the patients without pneumonitis ($1.28{\pm}0.31$, p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (${\beta}2$-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant. Conclusion: Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.

• The Journal of Internal Korean Medicine
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• v.39 no.1
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• pp.1-8
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• 2018

Objectives: This study seeks to investigate the effects of Gamidohongsamul-tang (GDT) on the Gene expression levels of eNOS, KLF2, ICAM-1 and VCAM-1 in HUVEC cells. Methods: HUVEC cells were treated at a concentration of 1, 10, 100 (${\mu}g/ml$) of Gamidohongsamul-tang (GDT). To measure the NOS, KLF2, ICAM-1 and VCAM-1 gene expression in HUVEC cells, the synthesized cDNA was subjected to polymerase chain reaction (PCR) and electrophoresis was performed to verify gene expression level. Results: 1. GDT significantly increased eNOS and KLF2 gene expression. 2. GDT significantly reduced ICAM-1 and VCAM-1 gene expression. Conclusions: These experiments suggest that Gamidohongsamul-tang (GDT) regulates gene expression related with anti-dyslipidemic effects in HUVEC cells. In order to clinically apply this to diseases related to dyslipidemia, such as cardiovascular disease, additional in vivo experiments are needed to verify the anti-dyslipidemic effects of GDT.