Eun-Sook Lee

Hallym University, Seoul, Seoul, South Korea

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Publications (6)16.62 Total impact

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    ABSTRACT: Adipokines have been implicated in the pathogenesis of atherosclerosis via pro-inflammatory mechanisms contributing to insulin resistance. The adipokine resistin causes endothelium dysfunction, which plays an important role in sustaining atherogenesis. This study investigated whether resistin induced expression of cell adhesion molecules and integrins in endothelial cells and THP-1 monocytes and whether such induction was attenuated by 1-20 μM caffeic acid. Resistin enhanced endothelial expression of vascular cell adhesion molecule 1 (VCAM-1), intercellular cell adhesion molecule 1 (ICAM-1), and E-selectin and monocyte expression of β1, β2, and α4 integrins. The enhancement of these proteins was diminished by caffeic acid with reduced THP-1 cell adhesion on activated endothelium. Caffeic acid at ≤20 μM demoted resistin-stimulated interleukin 8 (IL-8) production responsible for ICAM-1 and β2 integrin induction. The endothelial up-regulation of IL-8 secretion by resistin entailed toll-like receptor 4 (TLR4) activation, but caffeic acid diminished IL-8 production and TLR4 induction. Furthermore, caffeic acid encumbered resistin-activated nuclear factor κB (NF-κB) signaling. These results demonstrate that caffeic acid blocked monocyte trafficking to resistin-activated endothelium via disturbing NF-κB signaling responsive to IL-8. Therefore, caffeic acid may have therapeutic potential in preventing obesity-associated atherosclerosis.
    Journal of Agricultural and Food Chemistry 03/2012; 60(10):2730-9. · 2.91 Impact Factor
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    ABSTRACT: Foam cell formation is the hallmark of early atherosclerosis. Lipid uptake by scavenger receptors (SR) in macrophages initiates chronic proinflammatory cascades linked to atherosclerosis. It has been reported that the upregulation of cholesterol efflux may be protective in the development of atherosclerosis. Ellagic acid, a polyphenolic compound mostly found in berries, walnuts, and pomegranates, possesses antioxidative, growth-inhibiting and apoptosis-promoting activities in cancer cells. However, the antiatherogenic actions of ellagic acid are not well defined. The current study elucidated oxidized LDL handling of ellagic acid in J774A1 murine macrophages. Noncytotoxic ellagic acid suppressed SR-B1 induction and foam cell formation within 6 h after the stimulation of macrophages with oxidized LDL, confirmed by Oil red O staining of macrophages. Ellagic acid at ≤5 μmol/L upregulated PPARγ and ATP binding cassette transporter-1 in lipid-laden macrophages, all responsible for cholesterol efflux. In addition, 5 μmol/L ellagic acid accelerated expression and transcription of the nuclear receptor of liver X receptor-α highly implicated in the PPAR signaling. Furthermore, ellagic acid promoted cholesterol efflux in oxidized LDL-induced foam cells. These results provide new information that ellagic acid downregulated macrophage lipid uptake to block foam cell formation of macrophages and boosted cholesterol efflux in lipid-laden foam cells. Therefore, dietary and pharmacological interventions with berries rich in ellagic acid may be promising treatment strategies to interrupt the development of atherosclerosis.
    Journal of Nutrition 09/2011; 141(11):1931-7. · 4.20 Impact Factor
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    ABSTRACT: Bone-remodeling imbalance induced by decreased osteoblastogenesis and increased bone resorption is known to cause skeletal diseases such as osteoporosis. Silibinin is the major active constituent of silymarin, the mixture of flavonolignans extracted from blessed milk thistle (Silybum marianum). Numerous studies suggest that silibinin is a powerful antioxidant and has anti-hepatotoxic properties and anti-cancer effects against carcinoma cells. This study investigated that silibinin had bone-forming and osteoprotective effects in in vitro cell systems of murine osteoblastic MC3T3-E1 cells and RAW 264.7 murine macrophages. MC3T3-E1 cells were incubated in osteogenic media in the presence of 1-20 µM silibinin up to 15 days. Silibinin accelerated cell proliferation and promoted matrix mineralization by enhancing bone nodule formation by calcium deposits. In addition, silibinin furthered the induction of osteoblastogenic biomarkers of alkaline phosphatase, collagen type 1, connective tissue growth factor, and bone morphogenetic protein-2. Differentiated MC3T3-E1 cells enhanced secretion of receptor activator of nuclear factor-κB ligand (RANKL) essential for osteoclastogenesis, which was reversed by silibinin. On the other hand, RAW 264.7 cells were pre-incubated with 1-20 µM silibinin for 5 days in the presence of RANKL. Non-toxic silibinin markedly attenuated RANK transcription and intracellular adhesion molecule-1 expression elevated by RANKL, thereby suppressing the differentiation of macrophages to multi-nucleated osteoclasts. It was also found that silibinin retarded tartrate-resistant acid phosphatase and cathepsin K induction and matrix metalloproteinase-9 activity elevated by RANKL through disturbing TRAF6-c-Src signaling pathways. These results demonstrate that silibinin was a potential therapeutic agent promoting bone-forming osteoblastogenesis and encumbering osteoclastic bone resorption.
    Journal of Cellular Biochemistry 09/2011; 113(1):247-59. · 3.06 Impact Factor
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    ABSTRACT: Human leukocyte endothelial adhesion and transmigration occur in the early stage of the pathogenesis of atherosclerosis. Vascular endothelial cells are targeted by pro-inflammatory cytokines modulating many gene proteins responsible for cell adhesion, thrombosis and inflammatory responses. This study examined the potential of compound K to inhibit the pro-inflammatory cytokine TNF-α induction of monocyte adhesion onto TNF-α-activated human umbilical vein endothelial cells (HUVEC). HUVEC were cultured with 10ng/ml TNF-α with individual ginsenosides of Rb1, Rc, Re, Rh1 and compound K (CK). Ginsenosides at doses of ⩽50μM did not show any cytotoxicity. TNF-α induced THP-1 monocyte adhesion to HUVEC, and such induction was attenuated by Rh1 and CK. Consistently, CK suppressed TNF-α-induced expression of HUVEC adhesion molecules of VCAM-1, ICAM-1 and E-selectin, and also Rh1 showed a substantial inhibition. Rh1 and CK dampened induction of counter-receptors, α4/β1 integrin VLA-4 and αL/β2 integrin LFA-1 in TNF-α-treated THP-1 cells. Additionally, CK diminished THP-1 secretion of MMP-9 required during transmigration, inhibiting transendothelial migration of THP-1 cells. CK blunted TNF-α-promoted IL-8 secretion of HUVEC and CXCR1 expression of THP-1 monocytes. Furthermore, TNF-α-activated endothelial IκB phosphorylation and NF-κB nuclear translocation were disturbed by CK, and TNF-α induction of α4/β1 integrin was abrogated by the NF-κB inhibitor SN50. These results demonstrate that CK exerts anti-atherogenic activity with blocking leukocyte endothelial interaction and transmigration through negatively mediating NF-κB signaling.
    Chemico-biological interactions 08/2011; 194(1):13-22. · 2.46 Impact Factor
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    ABSTRACT: Development of diabetic nephropathy with fibrosis is associated with hypereglycemia-linked inflammation. Increased levels of proinflammatory factors have been found in diabetic patients with nephropathy. The present study was to test the hypothesis that isoangustone A, a novel compound present in licorice, can inhibit renal fibrosis and inflammation inflamed by high glucose (HG) in human mesangial cells through disturbing transforming growth factor β (TGF-β) and nuclear facor κB (NF-κB) pathways. Serum-starved mesangial cells were cultured in 33 mmol/L glucose media. Cells were treated with 1-20 μmol/L isoangustone A isolated from Glycyrrhiza uralensis licorice for three days. Exposure of cells to HG elevated connective tissue growth factor and collagen production, which was dose-dependently reversed by isoangustone A. Isoangustone A boosted HG-plummeted membrane type matrix metalloproteinase (MMP)-1 expression and diminished HG-elevated tissue inhibitor of MMP-2 expression. HG activated mesangial TGF-β1-SMAD-responsive signaling, which was repealed by ≥10 μmol/L isoangustone A. Furthermore, HG upregulated intracellular cell adhesion molecule-1 (ICAM-1) level and monocyte chemoattractant protein-1 (MCP-1) mRNA expression, and such increases were dose-dependently suppressed by isoangustone A most likely through hampering TGF-β signaling pathways. Blockade of NF-κB signaling appeared to be responsible for attenuating HG-triggered induction of ICAM-1 and MCP-1. Our findings provide the first evidence that isoangustone A dampens mesangial sclerosis associated with inflammation in response to HG through hindering TGF-β and NF-κB signaling.
    Experimental Biology and Medicine 03/2011; 236(4):435-44. · 2.80 Impact Factor
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    ABSTRACT: Oleanolic acid is a triterpenoid compound that is widely present in vegetables, medicinal herbs, and other plants and has potent antioxidant and antiinflammatory properties. However, the potential of oleanolic acid to offset obesity is not clear. This study tested the hypothesis that oleanolic acid suppresses the differentiation of 3T3-L1 adipocytes by downregulating cellular induction of peroxisome proliferators-activated receptor γ (PPARγ) and cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT) enhancer binding protein α (C/EBPα). The 3T3-L1 adipocytes were cultured and differentiated in Dulbecco modified Eagle medium containing 10% fetal bovine serum for 6 to 8 days in the absence and presence of 1 to 25 μmol/L oleanolic acid according to differentiating protocols. Nontoxic oleanolic acid, at 25 μmol/L or less, dose-dependently attenuated lipid accumulation in differentiated adipocytes as evidenced by Oil Red O staining. Western blot analysis showed that the induction of PPARγ and C/EBPα was markedly attenuated in differentiated and oleanolic acid-treated adipocytes at their transcriptional messenger RNA levels. Furthermore, this study examined whether oleanolic acid dampened the induction of visfatin, a proinflammatory and visceral fat-specific adipokine expressed in adipocytes. Visfatin expression was inhibited in differentiated adipocytes exposed to a PPARγ inhibitor GW9662. In addition, the visfatin production was significantly repressed in 25 μmol/L oleanolic acid-treated adipocytes, possibly through blocking PPARγ activation. These results demonstrate that oleanolic acid may be a promising agent to disturb adipocyte differentiation and suppress obesity-associated inflammation.
    Nutrition research (New York, N.Y.) 12/2010; 30(12):831-9. · 1.20 Impact Factor