• BMB Reports
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• v.49 no.1
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• pp.57-62
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• 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]

• 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.

• Korean Journal of Pharmacognosy
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• v.33 no.4 s.131
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• pp.343-351
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• 2002

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in the arteries. Monocyter/macrophages are involved in many aspects of the development of atherosclerotic plaques. It is known that the intercellular adhesion molecule-1(ICAM-1) expressed preferentially on endothelial cells of atherosclerotic plaque, promotes local adhesion and transendothelial migration of monocytes, neutrophils, and lymphocytes. Using the human promyelocytic leukemia HL-60 cell line, we investigated the inhibitory effects of methanol extracts of 175 natural plants on ICAM-1/LFA-1 mediated cell adhesion. Eight kinds of methanol extracts of tested plants inhibited PMA-induces homotypic aggregationof HL-60 cells without cytotoxicity at the concentration of $6.25\;{\mu}g/ml$. They were divided two fractions of $CHCI_3$ and $H_2O$ to use solvent partition. Among them, $CHCI_3$ extract $(1.0\;{\mu}g/ml)$ of Saururus chinensis and Chloranthus japonicus singificantly inhibited aggregation of HL-60 cells without cytotoxicity, respectively.

• International Journal of Oral Biology
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• v.30 no.1
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• pp.31-37
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• 2005

Treponema maltophilum, a Group IV oral spirochete, is associated with periodontitis and endodontic infections. In this study we analyzed the functional role of the major surface protein of this organism (MspA) in human gingival fibroblasts (HGFs). The full-length gene encoding MspA was cloned and expressed in Escherichia coli by using the expression vector pQE-30. The recombinant protein (rMspA) was purified by affinity chromatography with nickel-nitrilotriacetic acid agarose and possible contamination of E. coli endotoxin in rMspA was removed by using polymyxin B-agarose. rMspA significantly induced the expression of pro inflammatory cytokines like IL-6 and IL-8 and intercellular adhesion molecule (ICAM)-1 in HGFs, when analyzed by reverse transcription-PCR, flow cytometry, and enzyme-linked immunosorbent assay. Our results indicate that MspA of T. maltophilum may play an important role in amplifying the local immune response by upregulating the expression of proinflammatory cytokines and ICAM-1.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1167-1177
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• 1998

Background : Pulmonary tuberculosis is one of the diseases characterized granuloma formation which was controlled by cellular immune reactions. In the process of granulomatous changes, activated alveolar macrophages and T lymphocytes secrete many cytokines including interleukin-1 (IL-1), tumor necrosis factor-alpha(TNF-$\alpha$), interferon-gamma(IFN-$\gamma$) which mediate inflammatory reactions. Intercelluar adhesion molecule-1(ICAM-1) also known to major role player in inflammatory processes, and increased cellular expressions when endothelial cell was stimulated by IL-1, TNF and IFN. Method : To evaluate relationships among cellular immune reactions and clinical stages, pulmonary tuberculosis patients were classified into three groups according to their clinical stages including minimal, moderate and far advanced tuberculosis. TNF-$\alpha$ IFN-$\gamma$, sICAM-1 (soluble form of ICAM-1) were measured at the time of diagnosis and after 6-months anti-tuberculosis medications by radioimmuno assay or enzyme linked immunosolvent assay. Result : TNF-$\alpha$, IFN-$\gamma$, sICAM-1 were significantly increased in moderate and far advanced pulmonary tuberculosis patients but no meaningful changes in minimal staged patients. 6-months anti-tuberculosis medications reduced serum sICAM-1 levels significantly, related to clinical improvement but no significant changes were found in the serum levels of TNF-$\alpha$ and IFN-$\gamma$. In the point of correlations. positive ones revealed between TNF-$\alpha$ and sICAM-1, also between IFN-$\gamma$ and sICAM-1 but no correlation between TNF-$\alpha$ and IFN-$\gamma$. Conclusion : Measurement of serum sICAM-1 could be useful parameter to evaluate the severity of pulmonary tuberculosis and to monitor disease activities during anti-tuberculosis medications.

• Journal of Ginseng Research
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• v.43 no.1
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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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• v.28 no.5
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• pp.423-430
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• 2020

Telmisartan is an angiotensin-II receptor blocker and acts as a selective modulator of peroxisome proliferator-activated receptor gamma (PPARγ). Several studies have demonstrated that telmisartan ameliorates depression and memory dysfunction and reduces brain inflammation. We hypothesized that the beneficial effects of telmisartan on brain could be due to modulation of the blood-brain barrier (BBB) function. Here, we examined the effect of telmisartan on tumor necrosis factor alpha (TNF-α)-induced expression of intercellular adhesion molecule 1 (ICAM-1) which plays an important role in leukocyte transcytosis through the BBB. Telmisartan blocked TNF-α-induced ICAM-1 expression and leukocyte adhesion in U87MG human glioma cells but showed no effect on human brain microvascular endothelial cells. In U87MG cells, a PPAR antagonist, GW9662 did not block the effect of telmisartan on ICAM1 expression but rather potentiated. Moreover, GW9662 caused no change in TNF-α-induced ICAM-1 expression, suggesting no implication of PPARγ in the telmisartan effect. Further studies showed that telmisartan blocked TNF-α-induced activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and nuclear factorkappa B (NF-κB). In contrast, inhibitors of JNK, ERK1/2 and NF-κB but not p38, blocked ICAM-1 expression induced by TNF-α. Thus, our findings suggest that the beneficial effect of telmisartan is likely due to the reduction of astrocytic ICAM1 expression and leukocytes adhesion to astrocytes, and that this response was mediated by the inhibition of JNK/ERK1/2/NF-κB activation and in the PPAR-independent manner. In conclusion, this study enhances our understanding of the mechanism by which telmisartan exerts the beneficial brain function.

• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.3
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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.

• Journal of Life Science
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• v.23 no.10
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• pp.1199-1208
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• 2013

Fibroblastic reticular cells (FRCs) form the structural backbone of the T zone provide a guidance path for immigrating T cells in the lymph node (LN). FRCs may contribute directly to developing T-cell biology in the LN and allow analyses of fundamental aspects of FRC biology related to T cells. FRCs inhibited T-cell apoptosis, and FRC culture supernatants strongly induced the expression of Bcl-xL in T cells against doxorubicin. Coculture of FRC and T cells resulted in rearrangements of the actin cytoskeleton, as well as global changes in the morphology of the FRCs. In addition, when cocultured, the T cells adhered to the FRC monolayer, and the membrane intercellular adhesion molecule (ICAM)-1 was slightly increased by day-dependent manner. In contrast, the expression of soluble ICAM-1 was dramatically increased in a day-dependent manner. Several chemokines, such as CCL5, CXCL1, CXCL5, CXCL16, CCL8, CXCL13, and ICAM-1, and MMPs were expressed in FRCs sensed by tumor necrosis factor (TNF) families. Nuclear factor kappa B ($NF{\kappa}B$)-RelA of the $NF{\kappa}B$ canonical pathway was translocated into FRC nuclear by $TNF{\alpha}$. In contrast, p52 proteolyzed from p100, a counterpart of RelB of the noncanonical $NF{\kappa}B$ pathway, accumulated in the peripheral FRC nucleus by agonistic anti-$LT{\beta}R$ antibody. In summary, we propose a model in which FRCs engage in bidirectional crosstalk to increase the efficiency of T-cell biology. This cooperative feedback loop may help to maintain tissue integrity and function during immune responses.

• 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.