• Archives of Reconstructive Microsurgery
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• v.9 no.2
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• pp.190-198
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• 2000

본 연구는 백서 복직근피판에 있어 허혈-재혈류 손상에 미치는 prostaglandin E1(PGE-1)의 예방효과를 분석 실험하였으며, 그 기전으로 내피세포의 intercellular adhesion molecule-1(ICAM-1)이 down regulation 됨을 확인하였다. 기존의 PGE-1은 혈관 확장 및 혈소판 응고 저하 등의 기전으로 피판 이식술 후 주로 사용하였으나, 허혈-재혈류 손상 시에 PGE-1 역할에 대한 연구는 잘 알려진바 없다. 허혈-재혈류 손상에 대한 기전은 현재 여러 가설로 설명되고 있으나, 최근 내피 세포와 백혈구의 역할이 주목을 받고 있다. 장시간 허혈 상태의 피판은 재혈류시 백혈구가 내피세포에 접착함으로써 직간접적인 경로로 독소를 생성하며, 결국 내피세포 및 주변조직의 괴사로 이어진다. 본 연구는 면역조직학 염색을 통한 내피세포의 ICAM-1 발현 억제와 그로 인한 백혈구의 내피세포 접착 억제를 그 기전으로 볼 수 있었으며, PGE-1을 술 중 투여함으로써 피판의 생존율을 향상시킬 수 있었다.

• Journal of Life Science
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• v.17 no.8 s.88
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• pp.1152-1156
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• 2007

The Camella japonica flower(CJF) extract was studied for their anti-angiogenenic and anti-cell adhesion effect. CJF-extract inhibited the tube formation on human umbilical vein endotherial cells(HUVEC) with butanol extract by 70.2%, acetone extract by 54.2%, ethyl acetate extract by 37.0%, chloroform extract by 21.2%. Cell adhesion molecules were effectively suppressed at different concentration of CJF at 50, 100, 200 ug/well such as for intercellular adhesion molecule(ICAM) by 5.9%, 29.4% and 52.9%, for vascular cell adhesion molecule(VCAM) by 12.5%, 43.8% and 62.5%, for E-selectin by 7.1%, 21.4% and 35.7%, respectively. Signal molecules of vascular endotherial growth factor receptor 2(VEGFR2), ${/beta}$-catenin and PI3K are inhibited by different concentration of CJF at 10, 20 and 30 ${\mu}g/mL$ with western blot. Angiogenesis will be inhibited with suppressing NF-kB molecule resulted in signal molecules blocked by CJF. CJF will be useful materials for treatment of angiogenesis related diseases such as cancer, metastasis, rheumathioid arthritis and obesity.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.3
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• pp.155-160
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• 2002

It is not known whether gender differences play a role in susceptibility to ischemic acute renal failure. Thus, we examined if there were any differences in susceptibility between male and female mice to kidney ischemic injury, and if so, whether it is due to differences in mitogen activated protein kinases (MAPKs) or inflammatory responses to ischemia. Female mice were protected against kidney ischemia when compared with males. Thirty minutes of bilateral ischemia resulted in marked functional and morphological damages in males, but not in females. The ischemia-induced phosphorylation of c-jun N-terminal stress-activated protein kinases (JNKs) was higher in males than in females. Phosphorylation of extracellular signal-regulated kinases (ERKs) was lower in males than in females. Post- ischemia medullary infiltration of RAW 264.7 cell, a monocyte-macrophage cell, and intercellular adhesion molecule-1 (ICAM-1) were greater in males than in females. In conclusion, males were much more susceptible to ischemia than females. The enhanced propensity to ischemic injury in males was correlated with greater activation of JNKs, greater expression of ICAM-1, and greater trapping of leukocytes in the medulla.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5929-5934
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• 2013

Background: Primary brain tumors constitute a small percent of all malignant cancers, but their etiology remains poorly understood. ${\beta}3$ integrin (ITGB3) has been recognized to play influential roles in angiogenesis, tumor growth and metastasis. Intercellular adhesion molecule-1 (ICAM-1) is a surface glycoprotein important for tumor invasion and angiogenesis. The aim of this study was to investigate whether specific genetic polymorphisms of ICAM-1 and ITGB3 could be associated with brain cancer development and progression in a Turkish population. Our study is the first to our knowledge to investigate the relationship between brain tumor risk and ICAM-1 and ${\beta}3$ integrin gene polymorphisms. Materials and Methods: The study covered 92 patients with primary brain tumors and 92 age-matched healthy control subjects. Evaluation of ${\beta}3$ integrin (Leu33Pro (rs5918)) and ICAM-1 (R241G (rs1799969) and K469E (rs5498)) gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: According to results of our research, the A allele of the ICAM-1 R241G gene polymorphism appeared to be a risk factor for primary brain tumors (p<0.001). Similarly, the frequency of the A mutant allele of ICAM-1 R241G was statistically significant in patients with brain tumors classified as glioma (p<0.001). When allele and genotype distributions of ICAM-1 K469E, ICAM-1 R241G and ${\beta}3$ integrin Leu33Pro gene polymorphisms were evaluated with age, sex, and smoking, there were no statistically significant differences. Haplotype analysis revealed that the frequencies of GAC (rs1799969-rs5498-rs5918) and GAT (rs1799969-rs5498-rs5918) haplotypes were significantly lower in patients as compared with controls (p=0.001; p=0.036 respectively). Conclusions: This study provides the first evidence that ICAM-1 R241G SNP significantly contributes to the risk of primary brain tumors in a Turkish population. In addition, our results suggest that ICAM-1 R241G in combination ICAM-1 K469E may have protective effects against the development of brain cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.1
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• pp.27-38
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• 2021

Excessive salt intake induces hypertension, but several gamma-aminobutyric acid (GABA) supplements have been shown to reduce blood pressure. GABA-salt, a fermented salt by L. brevis BJ20 containing GABA was prepared through the post-fermentation with refined salt and the fermented GABA extract. We evaluated the effect of GABA-salt on hypertension in a high salt, high cholesterol diet induced mouse model. We analyzed type 1 macrophage (M1) polarization, the expression of M1 related cytokines, GABA receptor expression, endothelial cell (EC) dysfunction, vascular smooth muscle cell (VSMC) proliferation, and medial thicknesses in mice model. GABA-salt attenuated diet-induced blood pressure increases, M1 polarization, and TNF-α and inducible nitric oxide synthase (NOS) levels in mouse aortas, and in salt treated macrophages in vitro. Furthermore, GABA-salt induced higher GABAB receptor and endothelial NOS (eNOS) and eNOS phosphorylation levels than those observed in salt treated ECs. In addition, GABA-salt attenuated EC dysfunction by decreasing the levels of adhesion molecules (E-selectin, Intercellular Adhesion Molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1]) and of von Willebrand Factor and reduced EC death. GABA-salt also reduced diet-induced reductions in the levels of eNOS, phosphorylated eNOS, VSMC proliferation and medial thickening in mouse aortic tissues, and attenuated Endothelin-1 levels in salt treated VSMCs. In summary, GABA-salt reduced high salt, high cholesterol diet induced hypertension in our mouse model by reducing M1 polarization, EC dysfunction, and VSMC proliferation.

• Journal of Sasang Constitution and Immune Medicine
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• v.12 no.2
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• pp.171-183
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• 2000

1. Back ground and purpose An experimental study has done to examine the effect of defense and cure gastric mucasal damage of Mokdan-pijihwang-tang. 2. Methods Mice had intragastric injected with MJ extract before indomethacin treatment which induces homorrhage infarct and erosion artificially. Degree of lipid peroxidation, general morphology, change of mucous cell, the distribution of PNA, ICAM and distribution of apoptotic cell were objected. (Abbreviation) MJ : Mokdanpijihwang-tang, PNA : Peanut Agglutinin, ICAM : Intercellular Adhesion Molecule 3 Results 1) The degree of lipid peroxidation in INDO-group had increased conspicuously than control group. But the degree of lipid peroxidation in MJ-group had decreased than INDO-group and these decline had probability. 2) After indomethacin treatment, hemorrhage infarct and erosion had increased in stomach body. But in MJ-group, the configuration is normal, except the group intragastric injected with MJ extract at hour 24 before indomethacin treatment. 3) Surface mucous cell and neck mucous had disappeared in INDO-group. But in MJ-group tormal distribution had shown like control group except the group intragastric injected with MJ extract at hour 24 before indomethacin treatment. 4) PNA positive reaction had not shown in INDO-group. But medium PNA positive reaction had shown In Mj-group. 5) ICAM positive reacted cell had shown in INDO-group. The decrease of ICAM positive cell were shown than INDO-group. 6) A number of apoptotic cell was distributed in hemorrhagic erosion. A few number of apoptotic cell was distributed in MJ-group except some surface mucous. 4. Conclusion These results suggest that MJ has an effect on cure of gastric mucosal damage.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.4
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• pp.377-384
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• 2017

Activation of protein kinase C (PKC) is closely linked with endothelial dysfunction. However, the effect of $PKC{\beta}II$ on endothelial dysfunction has not been characterized in cultured endothelial cells. Here, using adenoviral $PKC{\beta}II$ gene transfer and pharmacological inhibitors, the role of $PKC{\beta}II$ on endothelial dysfucntion was investigated in cultured endothelial cells. Phorbol 12-myristate 13-acetate (PMA) increased reactive oxygen species (ROS), p66shc phosphorylation, intracellular adhesion molecule-1, and monocyte adhesion, which were inhibited by $PKC{\beta}i$ (10 nM), a selective inhibitor of $PKC{\beta}II$. PMA increased the phosphorylation of CREB and manganese superoxide dismutase (MnSOD), which were also inhibited by $PKC{\beta}i$. Gene silencing of CREB inhibited PMA-induced MnSOD expression, suggesting that CREB plays a key role in MnSOD expression. Gene silencing of $PKC{\beta}II$ inhibited PMA-induced mitochondrial ROS, MnSOD, and ICAM-1 expression. In contrast, overexpression of $PKC{\beta}II$ using adenoviral $PKC{\beta}II$ increased mitochondrial ROS, MnSOD, ICAM-1, and p66shc phosphorylation in cultured endothelial cells. Finally, $PKC{\beta}II$-induced ICAM-1 expression was inhibited by Mito-TEMPO, a mitochondrial ROS scavenger, suggesting the involvement of mitochondrial ROS in PKC-induced vascular inflammation. Taken together, the results suggest that $PKC{\beta}II$ plays an important role in PMA-induced endothelial dysfunction, and that the inhibition of $PKC{\beta}II$-dependent p66shc signaling acts as a therapeutic target for vascular inflammatory diseases.

• 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.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.264-269
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• 2013

Silymarin has been introduced fairly recently as a hepatoprotective agent. But its mechanisms of action still have not been well established. The aim of this study was to make alcoholic fatty liver model of rats in a short time and investigate silymarin's protective effects and possible mechanisms on alcoholic fatty liver for rats. The model of rat's alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. Histopathological changes were assessed by hematoxylin and eosin staining (HE). The activities of alanine transarninase (ALT) and aspartate aminotransferase (AST), the levels of total bilirubin (TBIL), total cholesterol (TC) and triglyceride (TG) in serum were detected with routine laboratory methods using an autoanalyzer. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in liver homogenates were measured by spectrophotometry. The TG content in liver tissue was determined by spectrophotometry. The expression of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in the liver were analyzed by immunohistochemistry. Silymarin effectively protected liver from alcohol-induced injury as evidenced by improving histological damage situation, reducing ALT and AST activities and TBIL level in serum, increasing SOD and GPx activities and decreasing MDA content in liver homogenates and reducing TG content in liver tissue. Additionally, silymarin markedly downregulated the expression of NF-${\kappa}B$ p65, ICAM-1 and IL-6 in liver tissue. In conclusion, Silymarin could protect against the liver injury caused by ethanol administration. The effect may be related to alleviating lipid peroxidation and inhibiting the expression of NF-${\kappa}B$.

• Journal of Periodontal and Implant Science
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• v.29 no.2
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• pp.333-350
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• 1999

The modulation of leukocyte cell surface adhesion molecules may influence the development of cellular events that determine the course of the inflammatory process. Direct interaction between activated T cells and monocytes resulted in a large production of $IL-1{\beta}$ by monocytes. In this reactions, adhesion molecules play an important part, yet the role of them in Tmonocytes interaction remain unclear. This study was undertaken in an effort to elucidate, 1) the influence of 1.25(OH)$_2D_3-induced$ differentiation on the monocyte responsiveness to direct contact with T lymphocytes, and 2) the role of adhesion molecules on the T-monocyte direct interaction. Initially, I observed that direct contact of monocyte cell line THP-1 with stimulated fixed T cell line HuT78 markedly induces IL-1${\beta}$ production by THP-1. $IL-1{\beta}$ production was higher when THP-1 had been previously exposed to 1.25(OH)$_2D_3$ as compared to control, with ${\alpha}$- 1.25(OH)$_2D_3$ dose-dependent and exposure time-dependent manner. It was shown that 1.25(OH)$_2D_3$ also increased the expression of ${\beta}_2$ integrin adhesion receptor Mac-1(CD11b/CD18) dose- and timedependently, but did not increase the expression of human leukocyte antigen- D(HLA-D) and intercellular adhesion molecule-1(ICAM-1). The $IL-1{\beta}$ producing activity of THP-1 cells correlated well with the ability to induce the Mac-1 expression on THP-1 surface. Monoclonal antibody raised against relevant cell surface glycoproteins on THP-1 were tested for their ability to block the response of THP-1 to T cells. Antibody to Mac-1 only partially blocked $IL-1{\beta}$ production by THP-1, whereas antibodies to ICAM-1 and HLA-D did not. These data indicate that regulation of Mac-1 expression on THP-1 cells can alter the responsiveness of these cells to contact by activated T cells, however other unknown structures on the THP-1 cells may be involved in this process also.