• Clinical and Experimental Pediatrics
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• 제48권6호
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• pp.640-648
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• 2005

목 적 : 가와사끼병은 여러 가지 면역학적 이상을 보이는 혈관염으로 혈관 내피세포의 면역학적 기전과 관련하여 세포부착 분자가 관여하는 것으로 알려져 있다. 본 연구는 가와사끼병에서 세포부착분자 sICAM-1과 sVCAM-1을 급성 발열기와 아급성기로 나누어 비교 분석하였고 이들의 심장병변과 관련된 임상적 의의를 찾고자 하였다. 방 법 : 2002년 1월부터 2004년 6월까지 중앙대학교 의료원 소아과에 전형적인 가와사끼병으로 입원한 32명을 대상으로 감마글로불린 투여 전 급성 발열기와 발병 2주의 아급성기의 Troponin T와 I, 심장 초음파 검사 소견, sICAM-1, sVCAM-1을 비교, 분석하였고, 가와사끼병이 아닌 급성 발열성 질환으로 입원한 16명을 대조군으로 하였다. 결 과 : sICAM-1 및 sVCAM-1은 급성 발열기 가와사끼병에서 대조군에 비하여 의미있게 증가하고(P=0.019, P=0.049) 특히 sICAM-1은 급성발열기에 비하여 아급성기때 의미있게 감소하였다(P=0.0015). 급성 발열기, 아급성기 모두에서 sICAM-1과 sVCAM-1은 상호간에 양의 상관관계를 나타내었다(P=0.0067, P=0.015). sICAM-1, sVCAM-1 모두 정맥용 감마글로불린 투여 횟수 및 반응성 여부를 반영하지는 못하며, 관상동맥 병변의 정도를 의미있게 반영하지는 못하였으나, sVCAM-1의 경우 급성 발열기 및 아급성기 모두 심염군에서 통계적으로 의미있게 증가하였다(P=0.025, P=0.014). 또한 급성 발열기 sVCAM-1과 Troponin T는 양의 상관관계를 나타내었다(r=0.63, P=0.00063). 결 론 : sICAM-1과 sVCAM-1은 가와사끼병의 병인에 중요한 역할을 하나 감마글로불린 투여 횟수 및 반응성 여부를 반영하지는 못하며, 가장 중요한 합병증인 관상동맥병변을 직접적으로는 반영하지는 못한다. 그러나 sVCAM-1의 경우 심염에 있어 중요한 역할을 하는 것으로 여겨진다. 이에 대해서는 다양한 세포부착분자에 대하여 가와사끼병에서의 면역학적인 기전에 대한 추가 연구가 있어야 할 것으로 생각한다.

• 대한한방부인과학회지
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• 제32권3호
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• pp.20-31
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• 2019

Objectives: The seeds from Arctium lappa have been considered for its various pharmacological properties, which include anti-carcinogenic, anti-inflammatory, anti-diabetic, and anti-viral activities. Methods: In the present study, we investigated the anti-inflammatory effect of the ethanol extract from the seeds of Arctium lappa L (EAL) on cytokine-induced vascular inflammation in human umbilical vein endothelial cells (HUVEC). Results: Pretreatment with EAL significantly decreased tumor necrosis factor alpha ($TNF-{\alpha}$)-induced cell adhesion molecules expression such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-selectin (E-selectin) in a dose-dependent manner. Cell adhesion assay showed that pretreatment with EAL suppressed HUVEC-monocyte adhesion by $TNF-{\alpha}$ over $1{\mu}g/ml$ concentration. We investigated the involvement of nuclear transcription factor kappa-B ($NF-{\kappa}B$) in $TNF-{\alpha}$-induced vascular inflammation. $NF-{\kappa}B$ p65 nuclear expression was induced by $TNF-{\alpha}$, however, pretreatment with EAL was attenuated that nuclear translocation. In cytoplasm, EAL was also attenuated $TNF-{\alpha}$-induced decrease of inhibitor of ${\kappa}B-{\alpha}$ ($I{\kappa}B-{\alpha}$) expression. Moreover, EAL significantly decreased $TNF-{\alpha}$-induced production of intracellular reactive oxygen species (ROS). Conclusions: Taken together, our findings suggest that seeds of Arctium lappa L could be a therapeutic herb for prevention of cardiovascular diseases throughout the inhibition of vascular endothelial inflammation.

• 생명과학회지
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• 제23권10호
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• pp.1199-1208
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• 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.

• Journal of Periodontal and Implant Science
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• 제29권2호
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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.

• 동의생리병리학회지
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• 제20권5호
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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.

• Journal of Periodontal and Implant Science
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• 제50권5호
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• pp.291-302
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• 2020

Purpose: The objective of this study was to investigate whether phelligridin D could reduce glucose-induced oxidative stress, attenuate the resulting inflammatory response, and restore the function of human periodontal ligament cells (HPDLCs). Methods: Primary HPDLCs were isolated from healthy human teeth and cultured. To investigate the effect of phelligridin D on glucose-induced oxidative stress, HPDLCs were treated with phelligridin D, various concentrations of glucose, and glucose oxidase. Glucose-induced oxidative stress, inflammatory molecules, osteoblast differentiation, and mineralization of the HPDLCs were measured by hydrogen peroxide (H₂O₂) generation, cellular viability, alkaline phosphatase (ALP) activity, alizarin red staining, and western blot analyses. Results: Glucose-induced oxidative stress led to increased production of H₂O₂, with negative impacts on cellular viability, ALP activity, and calcium deposition in HPDLCs. Furthermore, HPDLCs under glucose-induced oxidative stress showed induction of inflammatory molecules (intercellular adhesion molecule-1, vascular cell adhesion protein-1, tumor necrosis factor-alpha, interleukin-1-beta) and disturbances of osteogenic differentiation (bone morphogenetic protein-2, and -7, runt-related transcription factor-2), cementogenesis (cementum protein-1), and autophagy-related molecules (autophagy related 5, light chain 3 I/II, beclin-1). Phelligridin D restored all these molecules and maintained the function of HPDLCs even under glucose-induced oxidative stress. Conclusions: This study suggests that phelligridin D reduces the inflammation that results from glucose-induced oxidative stress and restores the function of HPDLCs (e.g., osteoblast differentiation) by upregulating autophagy.

• Journal of Ginseng Research
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• 제38권4호
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• pp.244-250
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• 2014

Background: Panax ginseng has distinct and impressive health benefits, such as improved blood pressure and immune system functioning. Rg3-enriched Korean Red Ginseng (REKRG) isolated from Korean Red Ginseng contains a high percentage of Rg3. Methods: In this study, we examined the effects of REKRG on endothelial cell nitric oxide synthase (eNOS) activation and adhesion molecules in endothelial cells and vascular function in rats. Results: REKRG dose-dependently increased eNOS phosphorylation and nitric oxide (NO) production in endothelial cells. In addition, REKRG markedly inhibited the tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-mediated induction of intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 expressions in endothelial cells. REKRG improved endothelium-dependent vasorelaxation in the Wistar-Kyoto (WKY) rat and spontaneously hypertensive rats (SHRs) compared with controls. Furthermore, REKRG treatment for 6 weeks increased serum NO levels and reduced the mean aortic intima-media thickness compared with controls. Conclusion: Taken together, these results suggest that REKRG increased vascular function and improved immune system functioning. Therefore, REKRG is a very useful food for preventing or improving various cardiovascular diseases.

• International Journal of Oral Biology
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• 제36권2호
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• pp.91-101
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• 2011

MspTL is the major surface protein of Treponema lecithinolyticum associated with periodontitis and endodontic infections. Our recent investigation revealed that MspTL induces proinflammatory cytokines and intercellular adhesion molecule 1 in THP-1 cells and periodontal ligament cells. In this study we conducted oligonucleotide microarray analysis to investigate the global transcriptional regulation in THP-1 cells stimulated with purified recombinant MspTL. MspTL upregulated the expression of 90 genes in THP-1 cells at least four fold, and the functions of these genes were categorized into adhesion, apoptosis/antiapoptosis, cell cycle/growth/differentiation, chemotaxis, cytoskeleton organization, immune response, molecular metabolism, proteolysis, signaling, and transcription. The majority of the modified genes are known to be NF-${\kappa}B$-responsive and interferon-stimulated genes (ISGs). The expression of 12 selected genes was confirmed by real-time RT-PCR. Because prostaglandin $E_2(PGE_2)$ is an important inflammatory mediator and Cox-2 was found to be induced by MspTL in the microarray analysis, we determined the level of $PGE_2$ in the culture supernatants of MspTL-treated cells and found that MspTL significantly increased $PGE_2$. Our results provide insight into the gene regulation of host cells in response to MspTL, and may contribute to the understanding of the molecular mechanism in periodontitis.

• Journal of Ginseng Research
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• 제43권1호
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• pp.95-104
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• 2019

Background: Oxidized low-density lipoprotein (ox-LDL) causes vascular endothelial cell inflammatory response and apoptosis and plays an important role in the development and progression of atherosclerosis. Ginsenoside compound K (CK), a metabolite produced by the hydrolysis of ginsenoside Rb1, possesses strong anti-inflammatory effects. However, whether or not CK protects ox-LDL-damaged endothelial cells and the potential mechanisms have not been elucidated. Methods: In our study, cell viability was tested using a 3-(4, 5-dimethylthiazol-2yl-)-2,5-diphenyl tetrazolium bromide (MTT) assay. Expression levels of interleukin-6, monocyte chemoattractant protein-1, tumor necrosis factor-${\alpha}$, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 were determined by enzyme-linked immunosorbent assay and Western blotting. Mitochondrial membrane potential (${\Delta}{\Psi}m$) was detected using JC-1. The cell apoptotic percentage was measured by the Annexin V/ propidium iodide (PI) assay, lactate dehydrogenase, and caspase-3 expression. Apoptosis-related proteins, nuclear factor $(NF)-{\kappa}B$, and mitogen-activated protein kinases (MAPK) signaling pathways protein expression were quantified by Western blotting. Results: Our results demonstrated that CK could ameliorate ox-LDL-induced human umbilical vein endothelial cells (HUVECs) inflammation and apoptosis, $NF-{\kappa}B$ nuclear translocation, and the phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Moreover, anisomycin, an activator of p38 and JNK, significantly abolished the anti-apoptotic effects of CK. Conclusion: These results demonstrate that CK prevents ox-LDL-induced HUVECs inflammation and apoptosis through inhibiting the $NF-{\kappa}B$, p38, and JNK MAPK signaling pathways. Thus, CK is a candidate drug for atherosclerosis treatment.

• Biomolecules & Therapeutics
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• 제29권3호
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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.