• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.199.1-199.1
• /
• 2003

In the course of our search for intercellular adhesion molecule-1 (ICAM-1)/leukocyte function-associated antigen-1 (LFA-1) mediated cell adhesion inhibitors from natural sources, new type of cell adhesion inhibitors were isolated from the MeOH extract of Saururus chinensis roots. On the basis of spectral evidence, the structures of the active compounds were identified as manassantin A and B. Manassantin A and B inhibited phorbol 12-myristate 13-acetate (PMA)-induced homotypic aggregation of the human promyelocytic leukemia HL-60 cells without cytotoxicity with MIC value of 1.0 and 5.5 nM, respectively. (omitted)

• Archives of Pharmacal Research
• /
• v.27 no.10
• /
• pp.1073-1079
• /
• 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.

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

• Biomolecules & Therapeutics
• /
• v.28 no.5
• /
• pp.423-430
• /
• 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.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.382.3-382.3
• /
• 2002

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in the arteries. Monocytes/macrophages are involved in many aspects of the development of atheroscleotic plaques. It is known that the intercellular adhesion molecule-1 (ICAM-1) expressed preferentially on endothelial cells of atheroscleotic 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 methoanol extracts of 175 plants on ICAM-1/LFA-1 mediated cell adhesion. Eight kinds of methanol extracts of tested plants inhibited PMA-induced homotypic aggregated cell adhesion. Eight kinds of methanol extracts of tested plants inhibited PMA-induced homotypic aggregation of HL-60 cells without cytotoxicity at the concentration of 6.25 ${\mu}$g/ml. $CHCl_3$ extracts (1.0 ${\mu}$g/ml) of Saururus chinensis and Chloranthus japonicus significantly inhibited agregation of HL-60 cells without cytoxicity.

• Journal of the East Asian Society of Dietary Life
• /
• v.24 no.3
• /
• pp.351-358
• /
• 2014

Pumpkin seed oil (PSO) was investigated for its parasite elimination activity and efficacy in treating disorders of the prostate gland and urinary bladder. We confirmed the composition of PSO and identified its ability to improve vessels. Gas chromatography coupled with mass spectrometric (GC-MS) system was used for PSO composition analysis. Cytotoxicity and cell proliferation were confirmed by Cell Counting Kit-8 (CCK-8) assay. Nitric oxide(NO) production was measured with Griess reagent, and intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 mRNA expression levels were measured by reverse transcription polymerase chain reaction (RT-PCR). As a result, PSO revealed the presence of several components such as linoleic acid, oleic acid, palmitic acid and stearic acid. Cytotoxic effects of PSO were not observed, and PSO increased nitric oxide production in human umbilical vein endothelial cells (HUVEC). Additionally, TNF-${\alpha}$-induced cell proliferation and ICAM-1 expression in HUVEC were inhibited by PSO treatment, whereas VCAM-1 expression was not significantly reduced. Taken together, these results show that PSO is worthy of study as a candidate food material for improvement of vascular disease.

• The Korean Journal of Physiology and Pharmacology
• /
• v.15 no.3
• /
• pp.157-162
• /
• 2011

Vascular inflammation process has been suggested to be an important risk factor in the development of atherosclerosis. Recently we reported that induction of peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$) selectively inhibits vascular cell adhesion molecule-1 (VCAM-1) but not intercellular cell adhesion molecule-1 (ICAM-1) in tumor necrosis factor (TNF)-${\alpha}$-activated human umbilical vein endothelial cells (HUVEC). In this study, we investigated whether genipin inhibits expression of cellular adhesion molecules, which is relevant to inflammation. Pretreatment with genipin reduced reactive oxygen species (ROS) production and expression of VCAM-1, but not ICAM-1 in TNF-${\alpha}$-activated HUVEC. Genipin dose- and time-dependently increased PPAR-${\gamma}$ expression and inhibited TNF-${\alpha}$-induced phosphorylation of Akt and PKC with different degrees. Finally, genipin prevented TNF-${\alpha}$-induced adhesion of U937 monocytic cells to HUVEC. Taken together, these results indicate that upregualtion of PPAR-${\gamma}$ by genipin selectively inhibits TNF-${\alpha}$-induced expression of VCAM-1, in which regulation of Akt and/or PKC play a key role. We concluded that genipin can be used for the treatment of cardiovascular disorders such as atherosclerosis.

• BMB Reports
• /
• v.49 no.1
• /
• 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]

• Biomolecules & Therapeutics
• /
• v.12 no.3
• /
• pp.133-137
• /
• 2004

Present review is built on base of research work on Ganoderma lucidum in our laboratory. A great deal of experimental evidence has suggested that the pharmacological activities of Ganoderma lucidum (Lingzhi) are related to anti-oxidative and free radical scavenging activity. The anti-oxidative and free radical scavenging effects of polysaccharides and triterpenoids isolated from Ganoderma lucidum in different oxidative injury models including tert-butylhydroperoxide (tBOOH)- damaged mice peritoneal macrophages, alloxan-induced diabetes, experimental liver injury models induced by carbon tetrachloride (CCl4), D-galactosamine (DGal) and Bacillus Calmette-Guerin (BCG) plus lipopolysaccharides (LPS) were investigated. It is also demonstrated that Lugu lingzhi, one of Ganoderma product, significantly inhibited LDL oxidation mediated by endothelial cells and decreased monocyte adhesion to endothelial cell (EC) induced by Oxidative low-density lipoprotein (ox-LDL) and advanced glycation endproducts (AGE). Lugulingzhi-treated serum could markedly inhibit the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-l) induced by ox-LDL and AGE.

• Nutrition Research and Practice
• /
• v.1 no.1
• /
• pp.65-69
• /
• 2007

We examined the associations between adiponectin or leptin and serum ICAM-1 levels in seventy-six hypercholesterolemic patients (mean age 59 yrs, 25 males and 51 females, LDL-cholesterol>=130mg/dL at screening). Blood lipid profiles and HOMA-IR derived from fasting glucose and insulin concentrations were determined. Serum levels of adiponectin, leptin and ICAM-1 were analyzed using ELISA The results showed that serum levels of leptin were positively associated with serum levels of ICAM-1 independent of age, sex and BMI (r=0.392, p<0.001). Serum levels of adiponectin were negatively associated with serum levels of ICAM-1 independent of age, sex and BMI (r=-0.343, p<0.005). Stepwise multiple linear regression analysis showed that serum leptin was an independent factor to be associated with serum ICAM-1 levels after adjusting for age, sex, BMI, alcohol intake, smoking status, blood lipids such as total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol and HOMA-IR (p<0.001). With respect to adiponectin, its association with serum ICAM-1 was attenuated but still significant when further adjustments were made for age, sex, BMI, alcohol intake, smoking status, blood lipids such as total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol and HOMA-IR (p<0.005). In conclusion, this study suggests that adiponectin and leptin are associated with endothelial derived inflammation.