• 대한한방내과학회지
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• 제39권1호
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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.

• BMB Reports
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• 제50권11호
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• pp.584-589
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• 2017

Intercellular adhesion molecule-1 (ICAM-1), which is induced by tumor necrosis factor (TNF)-${\alpha}$, contributes to the entry of immune cells into the site of inflammation in the skin. Here, we show that protein tyrosine phosphatase non-receptor type 21 (PTPN21) negatively regulates ICAM-1 expression in human keratinocytes. PTPN21 expression was transiently induced after stimulation with TNF-${\alpha}$. When overexpressed, PTPN21 inhibited the expression of ICAM-1 in HaCaT cells but PTPN21 C1108S, a phosphatase activity-inactive mutant, failed to inhibit ICAM-1 expression. Nuclear factor-${\kappa}B$ (NF-${\kappa}B$), a key transcription factor of ICAM-1 gene expression, was inhibited by PTPN21, but not by PTPN21 C1108S. PTPN21 directly dephosphorylated phospho-inhibitor of ${\kappa}B$ ($I{\kappa}B$)-kinase ${\beta}$ ($IKK{\beta}$) at Ser177/181. This dephosphorylation led to the stabilization of $I{\kappa}B{\alpha}$ and inhibition of NF-${\kappa}B$ activity. Taken together, our results suggest that PTPN21 could be a valuable molecular target for regulation of inflammation in the skin by dephosphorylating p-$IKK{\beta}$ and inhibiting NF-${\kappa}B$ signaling.

• Archives of Pharmacal Research
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• 제27권10호
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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.

• BMB Reports
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• 제46권8호
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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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• 제29권4호
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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 Chest Surgery
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• 제35권2호
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• pp.87-93
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• 2002

배경: 폐장 이식 수술 시 필연적으로 1~4 시간 이내에 나타나는 급성 허혈-재관류 손상 기 전에 세포간부착물질의 활성화가 중요한 역할을 하리라는 가설을 세우고 동물실험을 통해 폐장에서 허혈-재관류를 유도한 후 세포간부착물질의 활성화 정도와 장기의 기능을 동시에 평가하여 실제로 세포간부착물질의 증가에 의한 염증반응과 장기 기능 저하 현상 사이에 밀접한 관계가 있는지를 증명하고자 하였다. 대상 및 방법: 체중 15~20kg의 잡견 7마리를 사용하여 좌측 폐문부를 차단하여 좌측 폐 온혈 허혈을 100분간 유발시킨 후 재관류를 시켰다. 재관류 후 4시간 동안 우측 폐문부를 간헐적으로 차단하면서 허혈시킨 좌측 폐 단독으로의 가스교환능, 혈역학적 변수, 호흡 역학적 변수를 측정하고, 각 시간대별로 폐정맥혈 내 TNF-$\alpha$및 cICAM-1 농도를 측정하였다. 실험 종료 후 폐 조직 수분 함량, 조직 내 지방 산화물과 (malonedialdehide; MDA) ATP양을 측정하고, 광학 현미경 소견 및 면역 형광염색법으로 혈관내피세포의 ICAM-1 발현 양상을 관찰하였다. 결과: 동맥혈 산소 분압, 폐혈관저항 및 조직검사, 조직 내 MDA 농도와 ATP 농도는 폐손상 소견을 나타내었다. TNF-$\alpha$는 재관류 1시간에 8.76$\pm$2.37 ng/ml으로 최고치를 보인 후 빠르게 감소하였으나 cICAM-1은 변화가 없었다, 면역현광염색법을 이용한 혈관내피세로의 ICAM-1은 변화가 없었다. 면역형광염색법을 이용한 혈관내피세포의 ICAM-1염색은 2마리에서는 허혈 전, 후의 차이가 발견되지 않았으나, 3마리에서는 허혈-재관류의 손상 후 ICAM-1의 발현이 관찰되었고, 2마리에서는 그 발현 양상이 허혈 전에 비해 매우 뚜렷하였다. 결론: 이상의 결과에서 폐장의 허혈-재관류 손상 시 싸이토카인 과 세포부착물질이 증가하나 그 증가 시기에 차이가 있음을 밝혔다.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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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.

• 대한한의학회지
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• 제21권3호
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• pp.140-148
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• 2000

Objectives : This experiment was conducted to investigate the suppressive effects of Dangguijakyak-san and Wuelbigachul-tang on the expression of ICAM-l and ${\beta}1-integrin$, which mediate cell-cell or cell-matrix interaction, and on the proliferation of mesangial cells. Methods : After in vitro culturing of human mesangial cells with the supernatant which was obtained from the monocytes separated from human blood with Con-A, hydrocortisone, Dangguijakyak-san and Wuelbigachul-tang respectively, we evaluated suppressive effects by measuring the mesangial cell surface enzyme immunoassay or flow cytometry. Results : The results are summarized as follows: 1. Dangguijakyak-san and Wuelbigachul-tang induced marked suppressive effects on the mesangial cell proliferation in the 50% and 25% supernatant concentration stimulating experiments, but hydrocortisone had little effect in these experiments. 2. Dangguijakyak-san and Wuelbigachul-tang induced marked suppressive effects on ICAM-l and ${\beta}1-integrin$ expression, but were less effective than hydrocortisone was. Conclusions : Based on these results, Dangguijakyak-san and Wuelbigachul-tang were found to be effective in the suppression of mesangial cell proliferation and in ICAM-1 and ${\beta}1-integrin$ expression. Further in vitro investigations as conducted above, with the in vivo experiments reflected, may prove that Dangguijakyak-san and Wuelbigachul-tang contribute to the prevention of the glomerular disease.

• Biomolecules & Therapeutics
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• 제24권1호
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• pp.9-18
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• 2016

Bone matrix is properly maintained by osteoclasts and osteoblasts. In the tumor microenvironment, osteoclasts are increasingly differentiated by the various ligands and cytokines secreted from the metastasized cancer cells at the bone metastasis niche. The activated osteoclasts generate osteolytic lesions. For this reason, studies focusing on the differentiation of osteoclasts are important to reduce bone destruction by tumor metastasis. The N-myc downstream-regulated gene 2 (NDRG2) has been known to contribute to the suppression of tumor growth and metastasis, but the precise role of NDRG2 in osteoclast differentiation induced by cancer cells has not been elucidated. In this study, we demonstrate that NDRG2 expression in breast cancer cells has an inhibitory effect on osteoclast differentiation. RAW 264.7 cells, which are monocytic preosteoclast cells, treated with the conditioned media (CM) of murine breast cancer cells (4T1) expressing NDRG2 are less differentiated into the multinucleated osteoclast-like cells than those treated with the CM of 4T1-WT or 4T1-mock cells. Interestingly, 4T1 cells stably expressing NDRG2 showed a decreased mRNA and protein level of intercellular adhesion molecule 1 (ICAM1), which is known to enhance osteoclast maturation. Osteoclast differentiation was also reduced by ICAM1 knockdown in 4T1 cells. In addition, blocking the interaction between soluble ICAM1 and ICAM1 receptors significantly decreased osteoclastogenesis of RAW 264.7 cells in the tumor environment. Collectively, these results suggest that the reduction of ICAM1 expression by NDRG2 in breast cancer cells decreases osteoclast differentiation, and demonstrate that excessive bone resorption could be inhibited via ICAM1 down-regulation by NDRG2 expression.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.139.1-139.1
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• 2003

Since radiotherapy has been suspected to promote tumor metastasis and the presence of increase levels of adhesion molecules have implications for metastasis, we decided to investigate whether gamma-irradiation alters the expression of intercellular adhesion molecule-1 (ICAM-1) on neuroblastoma cells and the activities of relevant intracellular signaling molecules. In the present study, the relative of ICAM-1 expression under gamma-irradiated neuroblastoma cells were assessed by Western blot analysis. (omitted)