• KSBB Journal
• /
• 제28권4호
• /
• pp.230-237
• /
• 2013

Amyloid ${\beta}$ peptide (A${\beta}$) still best known as a molecule to cause Alzheimer's disease (AD). AD is characterized by the accumulation and deposition of A${\beta}$ within the brain, leading to neuronal cell loss and perturbation of synaptic function by causing free radical formation, inflammation and apoptosis. We investigated the inflammatory action of A${\beta}$ on two types of brain cells, neuronal cells (SH-SY5Y) and neuroglia cells (C6), and its mechanism. We measured the production of NO-iNOS, TNF-${\alpha}$, and ICAM-1 using RT-PCR and Western blot analysis less than the concentration of cytotoxic effects (> 70% survivability). A${\beta}$ had no effect on the production of NO and TNF-${\alpha}$, but significantly increases of iNOS and ICAM-1. Based on this, we suggest that the inflammatory effect of A${\beta}$ results from the action of ICAM-1 in neuronal cells, rather than the release of inflammatory mediators such as NO and TNF-${\alpha}$ in neuroglia cells. In addition, we confirmed whether p53 was related to the action of A${\beta}$ by using SH-SY5Y ($p53^{-/-}$) dominant cells. Neither the expression of p53 nor the cytotoxicity of SH-SY5Y ($p53^{-/-}$) cells were directly affected by A${\beta}$. However, ICAM-1 was not expressed in SH-SY5Y ($p53^{-/-}$) cells. This means that p53- independent pathway exists in the expression of ICAM-1 by A${\beta}$ while p53 plays a role as an on-and-off switch.

• The Korean Journal of Physiology and Pharmacology
• /
• 제15권5호
• /
• pp.251-258
• /
• 2011

Here we have investigated how lactosylceramide (LacCer) modulates gene expression of adhesion molecules in TNF-${\alpha}$ and IFN ${\gamma}$ (CM)-stimulated astrocytes. We have observed that stimulation of astrocytes with CM increased the gene expression of ICAM-1 and VCAM-1. D-Threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) and N-butyldeoxynojirimycin (NBDNJ), inhibitors of glucosylceramide synthase (GLS) and LacCer synthase (galactosyltransferase, GalT-2), inhibited the gene expression of ICAM-1 and VCAM-1 and activation of their gene promoter induced by CM, which were reversed by exogenously supplied LacCer. Silencing of GalT-2 gene using its antisense oligonucleotides also attenuated CM-induced ICAM-1 and VCAM-1 expression, which were reversed by LacCer. PDMP treatment and silencing of GalT-2 gene significantly reduced CM-induced luciferase activities in NF-${\kappa}B$, AP-1, GAS, and STAT-3 luciferase vectors-transfected cells. In addition, LacCer reversed the inhibition of NF-${\kappa}B$ and STAT-1 luciferase activities by PDMP. Taken together, our results suggest that LacCer may play a crucial role in the expression of ICAM-1 and VCAM-1 via modulating transcription factors, such as NF-${\kappa}B$, AP-1, STAT-1, and STAT-3 in CM-stimulated astrocytes.

• 대한한방내과학회지
• /
• 제41권4호
• /
• pp.668-675
• /
• 2020

Objectives: The aim of this study was to compare the effects of Galkunhwanglyeonhwanggum-tang (GGT), and Sopunghwalhyeol-tang (SPT) on gene expression of MCP-1, ICAM-1, VCAM-1, and eNOS in human umbilical vein endothelial cells (HUVECs). Methods: HUVECs were treated with GGT and SPT at concentrations of 50, 100, and 200 ㎍/mL. Gene expression of MCP-1, ICAM-1, VCAM-1, and eNOS in HUVECs was analyzed by the polymerase chain reaction (PCR), and electrophoresis was performed to verify the gene expression level. Results: 1. MCP-1 gene expression was more strongly decreased by SPT than by GGT. 2. ICAM-1 and VCAM-1 gene expressions were more strongly decreased by SPT than by GGT 3. GGT significantly increased eNOS gene expression, but SPT did not. Conclusions: These findings suggest that GGT and SPT regulate gene expression related to anti-inflammatory effects in HUVECs. Clinical application of these Korean medicines to diseases related to dyslipidemia, such as cardiovascular disease, will require additional in vivo experiments to verify the anti-inflammatory effects of GGT and SPT.

• 대한한의학회지
• /
• 제43권3호
• /
• pp.106-121
• /
• 2022

Objectives: The purpose of this study was to investigate the anti-inflammatory effect of Cornus Officinalis fruit extract(CE) and Cornus Officinalis Fruit Cheonghyeol Plus(CCP) in Human Umbilical Vein Endothelial Cell. Methods: We measured cell viability of CE, CCP and treated HUVEC with TNF-α. We measured the mRNA expression levels of KLF2, eNOS, MCP-1, ICAM-1, VCAM-1, the protein expression levels of KLF2, eNOS, MCP-1, ICAM-1, VCAM-1, and the protein phosphorylation level of ERK, JNK, p38 and the biomarker expression levels of MCP-1, ICAM-1, VCAM-1. Results: 1.CE incresed the mRNA, protein expression levels of KLF2, eNOS at concentrations of 100㎍/㎖ compared to the control group. CE decresed the mRNA, protein and biomarker expression levels of MCP-1,ICAM-1,VCAM-1 at concentrations of 100㎍/㎖ compared to the control group. CE decresed the protein phosphorylation level of p38 at concentrations of 100㎍/㎖ compared to the control group. 2. CCP incresed the mRNA, protein expression levels of KLF2, eNOS at concentrations of 100㎍/㎖ or more compared to the control group. CCP decresed the mRNA, protein and biomarker expression levels of MCP-1, ICAM-1, VCAM-1 at concentrations of 100㎍/㎖ or more compared to the control group. CCP decresed the protein phosphorylation level of ERK at concentrations of 100㎍/㎖ or more, p38 at concentrations of 200㎍/㎖ or more, and JNK at concentrations of 400㎍/㎖ compared to the control group. Conclusions: These results present that CE and CCP has anti-inflammatory effect in HUVEC. So, it could help treat or prevent inflammation in vein caused by dyslipidemia and contribute prevention of cardiovascular and cerebrovascular cerebrovascular diseases.

• BMB Reports
• /
• 제49권1호
• /
• pp.57-62
• /
• 2016

Up-regulation of adhesion molecules plays an important role in the infiltration of leukocytes into the skin during the development of various inflammatory skin diseases, such as atopic dermatitis. In this study, we investigated the modulatory effects of 2,3-dimethoxy-2′-hydroxychalcone (DMHC) on tumor necrosis factor (TNF)-α-induced intercellular adhesion molecule-1 (ICAM-1) expression and monocyte adhesiveness, as well as the molecular mechanisms underlying its action in the HaCaT human keratinocyte cell line. Pre-treating HaCaT cells with DMHC significantly suppressed TNF-α-induced ICAM-1 expression and subsequent monocyte adhesiveness. DMHC inhibited TNF-α-induced activation of NF-ᴋB. In addition, DMHC induced HO-1 expression as well as NRF2 activation. Furthermore, HO-1 knockdown using siRNA reversed the inhibitory effect of DMHC on TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes. These results suggest that DMHC may inhibit TNF-α-induced ICAM-1 expression and adhesion of monocytes to keratinocytes by suppressing the signaling cascades leading to NF-ᴋB activation and inducing HO-1 expression in keratinocytes. [BMB Reports 2016; 49(1): 57-62]

• The Korean Journal of Physiology and Pharmacology
• /
• 제9권2호
• /
• pp.109-115
• /
• 2005

Endothelial activation and subsequent recruitment of inflammatory cells are important steps in atherogenesis. The increased levels of cell adhesion molecules (CAM) have been identified in diabetic vasculatures, but the underlying mechanisms remain unclear. To determine the relationship among vascular production of superoxide, expression of CAM and diabetes, superoxide generation and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E- and P-selectin in the aorta from control (C57BL/6J) and diabetic mice (ob/ob) were measured. In situ staining for superoxide using dihydroethidium showed an increased superoxide production in diabetic aorta, accompanied with an enhanced NAD(P)H oxidase activity. Immunohistochemical analysis revealed that the endothelial expression of ICAM-1 ($3.5{\pm}0.4$) and VCAM-1 ($3.8{\pm}0.3$) in diabetic aorta was significantly higher than those in control aorta ($0.9{\pm}0.5$ and $1.6{\pm}0.3$, respectively), accompanied with the enhanced expression of gp91phox, a membrane subunit of NAD(P)H oixdase. Furthermore, there was a strong positive correlation (r=0.89, P＜0.01 in ICAM-1 and r=0.88, P＜0.01 in VCAM-1) between ICAM-1/VCAM-1 expression and vascular production of superoxide. The present data indicate that the increased production of superoxide via NAD(P)H oxidase may explain the enhanced expression of CAM in diabetic vasculatures.

• 대한한의학회지
• /
• 제21권3호
• /
• pp.40-50
• /
• 2000

Objectives : The progression of renal disease can be identified as a glomerulosclerosis by histological examination, and the basic mechanism of glomerulosclerosis is mesangial cell proliferation and mesangial matrix accumulation. ICAM-1, ${\beta}1-integrin$ and MHC-class II are known to attribute to the progression of glomerulosclerosis. They mediate cell-cell or cell-matrix interactions and are expressed in response to injury and inflammation. Up to now, there have been few satisfactory regimens to treat glomerular diseases except minimal change nephrotic syndrome, which can be improved by steroid therapy. Studies were performed in order to investigate whether Jinmu-tang has suppressive effects on some factors associated with the progression of glomerular disease, mesangial cell proliferation, fibronectin synthesis, ICAM-1, ${\beta}1-integrin$ and MHC-class II expression. Methods : Studies were performed with the method of surface enzyme immunoassays or flow cytometry after addition of peripheral blood mononuclear cells(PBMC) supernatants treated with Jinmu-tang, using the cultured human mesangial cells. Results : 1. The suppressive effect of Jinmu-tang on mesangial cell proliferation was higher than that of hydrocortisone. 2. Jinmu-tang has some suppressive effects on fibronectin synthesis, ICAM-1, expression, ${\beta}1-integrin$ expression and MHC-class II expression of mesangial cells, but was lower than hydrocortisone. Conclusions : Jinmu-tang generally shows some immunosuppressive effects. We carefully suggest that the above prescription may be applied to prevent the progression of renal disease or can be used as an adjuvant of or a substitute for steroid therapy.

• 대한기관식도과학회지
• /
• 제10권1호
• /
• pp.35-40
• /
• 2004

Adhesion molecules have been implicated in tumor progression. In this study, we aimed to investigate serum soluble intercellular adhesion molecule-1 (ICAM-1) and sialic acid (SA) levels in oral cavity cancer and laryngeal cancer and correlate their levels with cancer progression. Method : The sera from 31 patients with advanced oral cavity cancer (5 at stage III, 10 at stage IV) and advanced laryngeal cancer (1 at stage III, 15 at stage IV) were extracted before treatment. The concentrations of ICAM-1 was measured by Endogen kit (measured absorbance at 490nm) and the concentration of SA was measured by Roche kit (measured absorbance at 550nm). Respectively, gained data was compared with those from a control group (n=12). Result : Mean serum ICAM-1 and SA levels were found to be higher in oral cavity cancer group and laryngeal cancer group than control group. But statistical meaning was at SA (p<0.001, oral cavity cancer and laryngeal cancer versus control). Conclusion : These data reveal that the significant correlations serum SA level in advanced oral cavity cancer and laryngeal cancer. Serum ICAM-1 level was higher at advanced oral cavity cancer and laryngeal cancer than at control group but that was not significant.

• 대한바이러스학회지
• /
• 제26권1호
• /
• pp.47-58
• /
• 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.

• 생명과학회지
• /
• 제23권10호
• /
• pp.1199-1208
• /
• 2013

Fibroblastic reticular cells (FRC)는 림프절 T세포 지역에 구조적 골격 형성을 하며 유입 T 세포의 안내길을 제공한다. FRC는 림프절에서 T세포 생물학 발달에 기여한다. 따라서, 이것이 FRC와 T세포 사이에서 FRC의 세포생물학적 근본 기능을 알아보게 하였다. FRC 배양 상등액은 T세포 사멸을 저해하였다. FRC 상등액은 doxorubicin에 대하여 T세포에 Bcl-xL의 발현을 증가시켰다. FRC와 T세포의 공배양은 FRC의 액틴 골격의 변화와 형태적 변화를 유도하였다. 또한, FRC와 T세포의 공배양은 T 세포가 FRC 단일층에 부착하는 결과를 유도하였고 막결합형 intercellular adhesion molecule (ICAM)-1 단백질의 발현은 약간 증가한 반면 용해성 ICAM-1 (sICAM-1) 발현은 시간 의존적으로 드라마틱하게 증가하였다. FRC는 T세포에 의해 분비되는 tumor necrosis factor (TNF) 패밀리들에 의해 CCL5, CXCL1, CXCL5, CXCL16, CCL8, CXCL13와 같은 케모카인들과 ICAM-1 그리고 MMPs의 발현량을 증가시켰다. $TNF{\alpha}$가 FRC에 처리 되었을때 $NF{\kappa}B$ canonical pathway의 RelA는 핵으로 전좌 되었지만, agonistic anti-$LT{\beta}R$ antibody로 처리된 FRC에서 non-canonical $NF{\kappa}B$ pathway의 RelB의 카운터 파트너인 p100의 분해산물 p52는 핵주변부로 축적되었다. 결론적으로 FRC는 FRC와 T세포 양방향 협력을 통해 T세포 생물학적 기능을 증진한다. 이러한 상호협력 관계는 면역반응 동안 조직의 통합성과 기능을 유지하는데 도움을 줄 것으로 사료된다.