• Nutrition Research and Practice
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• v.10 no.4
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• pp.377-384
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• 2016

BACKGROUND/OBJECTIVES: Resveratrol, a natural polyphenol, has multiple functions in cellular responses including apoptosis, survival, and differentiation. It also participates in the regulation of inflammatory response and oxidative stress. MicroRNA-Let-7A (miR-Let7A), known as a tumor suppressor miRNA, was recently reported to play a crucial role in both inflammation and apoptosis. Therefore, we examined involvement of miR-Let7A in the modulation of inflammation and cell survival/apoptosis regulated by resveratrol. MATERIALS/METHODS: mRNA expression of pro-/anti-inflammatory cytokines and sirtuin 1 (SIRT1), and protein expression of apoptosis signal-regulating kinase 1 (ASK1), p-ASK1, and caspase-3 and cleaved caspase-3 were measured, and cell viability and Hoechst/PI staining for apoptosis were observed in Lipopolysaccharide (LPS)-stimulated human THP-1 macrophages with the treatment of resveratrol and/or miR-Let7A overexpression. RESULTS: Pre-treatment with resveratrol ($25-200{\mu}M$) resulted in significant recovery of the reduced cell viabilities under LPS-induced inflammatory condition and in markedly increased expression of miR-Let7A in non-stimulated or LPS-stimulated cells. Increased mRNA levels of tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6 induced by LPS were significantly attenuated, and decreased levels of IL-10 and brain-derived neurotrophic factor were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. Decreased expression of IL-4 mRNA by LPS stimulation was also significantly increased by miR-Let7A overexpression co-treated with resveratrol. In addition, decreased SIRT1 mRNA levels, and increased p-ASK1 levels and PI-positive cells by LPS stimulation were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. CONCLUSIONS: miR-Let7A may be involved in the inflammatory response and cell survival/apoptosis modulated by resveratrol in human THP-1 macrophages.

• Journal of Life Science
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• v.27 no.5
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• pp.553-560
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• 2017

Fermented garlic extract (FGE) is a well-known functional food containing cycloalliin. Here we tested if FGE has an effect on the vascular system. We found that FGE had an effect on monocytic adhesion to endothelial cells, which occurs at the initial step of processes of inflammation. From dose-dependent experiments, 0.1 to $1{\mu}g/ml$ of FGE appeared to inhibit lipopolysaccharide (LPS)-enhanced heterotypic cell adhesion between THP-1 and BAECs. This result indicates that FGE blocks vascular inflammation. Then we found that FGE activates eNOS and Akt in BAECs. The phosphorylation of eNOS was maximally elevated 10 min after FGE treatment. Parallely, the phosphorylation of Akt was also maximally increased 10 min after FGE treatment. Consistently, it was found that FGE enhanced the production of nitric oxide. We then examined whether NO mediates THP-1 cell adhesion to BAECs. Both Akt and eNOS inhibitors appeared to reverse an inhibitory effect of FGE. These findings indicate that FGE inhibits LPS-enhanced heterotypic cell adhesion via Akt and eNOS. In conclusion, FGE plays an important role in prevention of inflammatory diseases.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.3
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• pp.385-392
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• 2011

Although monoculture methods have been remarkably useful due to their simplicity, they have serious limitation because of the different types of cells communication with each other in many physiological situations. We demonstrated levels of markers of endothelial dysfunction such as tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-1$\beta$ (IL-1$\beta$) as well as stimulation of receptor of advanced glycation endproducts (AGEs) on monoand co-culture system such as only monocyte (THP-1) cultivation system, only endothelial cell (HUVEC) cultivation system, and co-cultivation system of THP-1 and HUVEC. The mRNA levels of TNF-$\alpha$ and IL-1$\beta$ on HUVEC increased by the co-culture with monocyte after 4 hr at 100 ${\mu}g/mL$ glyceraldehyde-AGE. The secreted protein contents into medium of TNF-$\alpha$ and IL-1$\beta$ increased after 8 hr approximately 2~2.5 times compared to mono-cultivation. In contrast, the mRNA level of receptor of AGE (RAGE) was relatively insensitive on the co-culture system. The mediators by which monocytes activate endothelial cell have not been fully elucidated. In this study we confirmed production of soluble cytokines such as TNF-$\alpha$ and IL-1$\beta$ by monocytes. Use of monocyte conditioned medium, which contains both cytokines, can activate endothelial cell.

• Biomedical Science Letters
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• v.26 no.4
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• pp.256-266
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• 2020

Carboxypeptidase D (CPD) is a zinc-dependent protease, which is highly expressed in macrophages, and is thought to participate in inflammatory processes. In the present study, we investigated the possible regulatory effect of all-trans retinoic acid (ATRA), which is an active form of vitamin A and plays a critical regulatory role in both the innate and adaptive immunity, on CPD expression and secretion in human monocytic THP-1 cells. CPD mRNA expression first increased, from a concentration as low as 10 nM ATRA to a maximum level of expression, at 1 μM. ATRA enhanced intracellular CPD expression in a time- and concentration-dependent manner but did not affect cell surface CPD expression. Interestingly, 9-cis-RA did not affect CPD expression. Additionally, an experiment with RAR/RXR selective agonist or antagonists demonstrated that ATRA-induced enhancement of CPD expression was RAR/RXR dependent. ATRA also enhanced CPD secretion from THP-1 cells; however, this enhancement was RAR/RXR-independent. The anti-inflammatory agent dexamethasone reversed ATRA-induced enhancement of CPD expression and secretion. Our results suggest ATRA exerts regulatory effects on expression and secretion of CPD in human monocytes, and ATRA-induced CPD secretion may be associated with inflammatory response.

• Journal of Marine Bioscience and Biotechnology
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• v.2 no.4
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• pp.250-256
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• 2007

The present study purified two noncyclic triterpenoids, compound 1 and compound 2, that intervene interaction of ICAM-1 and LFA-1 from ethanol extracts of Alpinia katsumadai. The compound 1 and 2 inhibited adherence of sICAM-1 to THP-1 cells with an $IC_{50}$ of $7.59{\mu}g/m{\ell}$ 및 $6.98{\mu}g/m{\ell}$, respectively, without affecting viability of the cells. The compound 1 and 2 also inhibited interaction of CHO-ICAM-1 cells with THP-1 cells with an $IC_{50}$ $6.7{\mu}g/m{\ell}$ 및 $5.5{\mu}g/m{\ell}$, respectively. These findings suggest that the noncyclic triterpenoids from Alpinia katsumadai have inhibitory activities against cell adherent molecules. The present study proposes that noncyclic triterpenoids from Alpinia katsumadai can applied to therapeutic approaches to the diseases that are associated with adhesion of inflammatory cells.

• IMMUNE NETWORK
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• v.4 no.2
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• pp.116-122
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• 2004

Background: LIGHT (TNFSF14) is a member of tumor necrosis factor superfamily and is the ligand for TR2 (TNFRSF14/HVEM). LIGHT is known to have proinflammatory roles in atherosclerosis. Methods: To find out the expression pattern of LIGHT in atherosclerotic plaques, immunohistochemical analysis was performed on human carotid atherosclerotic plaque specimens. LIGHT induced atherogenic events using human monocytic cell line THP-1 were also investigated. Results: Immunohistochemical analysis revealed expression of LIGHT and TR2 in foam cell rich regions in the atherosclerotic plaques. Double immunohistochemical analysis further confirmed the expression of LIGHT in foam cells. Stimulation of THP-1 cells, which express TR2, with either recombinant LIGHT or immobilized anti-TR2 monoclonal antibody induced interleukin-8 and matrix metalloproteinase(MMP)-9. Electrophoretic mobility shift assay demonstrated that LIGHT induces nuclear localization of transcription factor, nuclear factor $(NF)-{\kappa}B$. LIGHT induced activation of MMP-9 is mediated by $NF-{\kappa}B$, since treatment of THP-1 cells with the $NF-{\kappa}B$ inhibitor PDTC (pyrrolidine dithiocarbamate) completely blocked the activation of MMP-9. Conclusion: These data indicate that LIGHT is expressed in foam cells in atherosclerotic plaques and is involved in atherogenesis through activation of pro-atherogenic cytokine IL-8 and destabilization of plaque by inducing matrix degrading enzyme.

• Parasites, Hosts and Diseases
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• v.51 no.1
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• pp.85-92
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• 2013

IL-23 and IL-12 are structurally similar and critical for the generation of efficient cellular immune responses. Toxoplasma gondii induces a strong cell-mediated immune response. However, little is known about IL-23 secretion profiles in T. gondii-infected immune cells in connection with IL-12. We compared the patterns of IL-23 and IL-12 production by THP-1 human monocytic cells in response to stimulation with live or heat-killed T. gondii tachyzoites, or with equivalent quantities of either T. gondii excretory/secretory proteins (ESP) or soluble tachyzoite antigen (STAg). IL-23 and IL-12 were significantly increased from 6 hr after stimulation with T. gondii antigens, and their secretions were increased with parasite dose-dependent manner. IL-23 concentrations were significantly higher than those of IL-12 at the same multiplicity of infection. IL-23 secretion induced by live parasites was significantly higher than that by heat-killed parasites, ESP, or STAg, whereas IL-12 secretion by live parasite was similar to those of ESP or STAg. However, the lowest levels of both cytokines were at stimulation with heat-killed parasites. These data indicate that IL-23 secretion patterns by stimulation with various kinds of T. gondii antigens at THP-1 monocytic cells are similar to those of IL-12, even though the levels of IL-23 induction were significantly higher than those of IL-12. The detailed kinetics induced by each T. gondii antigen were different from each other.

• Journal of Oriental Neuropsychiatry
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• v.15 no.2
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• pp.103-118
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• 2004

Objective : This experiment was designed to investigate the effect of KongJin-dan(KJD) on the Alzheimer's disease. Method : The effects of KJD on $LI-1{\beta}$, IL-6, $TNF-{\alpha}$, amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 and THP-1 cell treated by CT105 and AChE activity, APP production of PC-12 cell lysate treated by CT105 were investigated, respectively. Results : 1. KJD suppressed $LI-1{\beta}$, IL-6, $TNF-{\alpha}$, APP, AChE, GFAP mRNA in THP-1 and PC-12 cell treated by CT105. 2. KJD suppressed AChE activity and production of APP significantly in cell lysate of PC-12 cell treated by CT105. Conclusions : This study shows that KJD might be usefully applied for prevention and treatment of Alzheimer's disease.

• The Journal of Korean Medicine
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• v.38 no.2
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• pp.53-60
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• 2017

Objectives: Beakdugu-tang (BDGT) consists of three medicinal herbs, and this prescription has long been used in treatment of various digestant problem in Korea. In this study, we designed to clarify mechanisms by which Korean traditional digestive medicine, BDGT, may exert anti-hepatic steatosis effects via improved insulin resistance cell model in human hepatocellular carcinoma (HepG2) and monocyte (THP-1). Materials and methods: The preparation of BDGT and constituents were extracted with 70% ethanol. HepG2 and THP-1 were treated with different concentrations of BDGT and constituents in the presence and absence of stimulants such as free fatty acids (FFAs) and oxidized low-density lipoprotein (ox-LDL), respectively. Results: The BDGT and its constituents inhibited the FFAs-stimulated lipid accumulation in HepG2 cells. Ethanol extracts of Amomum cardamomum (ACE) improved the ox-LDL induced insulin resistance in THP-1 cells. Also, treatment of monocytic cells with ACE increased anti-hepatic steatosis related gene levels including ABCA, ABCG and SR-B1. Conclusion: The results suggest that the ethanol extract of BDGT and its constituents potently inhibit the FFAs- and ox-LDL induced liver steatosis via improved insulin resistance.

• Journal of Acupuncture Research
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• v.40 no.4
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• pp.368-376
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• 2023

Background: Although bee venom (BV) has clinical benefits in osteoarthritis and rheumatoid arthritis, it has not been tested as treatment for gouty arthritis. Moreover, in vitro, BV has been proven to exhibit anti-inflammatory and positive effects on osteoarthritis, but only limited evidence can confirm its beneficial effects on gout. Thus, this study aims to assess the anti-inflammatory effects of BV on monosodium urate (MSU)-induced THP-1 monocytes. Methods: THP-1 monocytes were differentiated into mature macrophages using phorbol 12-myristate 13-acetate (PMA) and pretreated for 6 hours with BV and a Caspase-1 inhibitor in a physiologically achievable range of concentrations (BV, 0.1-1 ㎍/mL; Caspase-1 inhibitor, 1-10 μM), followed by MSU crystal stimulation for 24 hours. The secretions of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-6, IL-8, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) were increased in the MSU crystal-stimulated THP-1 cells. Results: Caspase-1 inhibitors suppressed the production of all mediators in a dose-dependent manner. BV worked on equal terms with Caspase-1 inhibitors and showed more satisfactory effects on TNF-α, PGE2, COX-2, and inducible nitric oxide synthase (iNOS). Moreover, the western blot analysis revealed that BV regulated the transcriptional levels of these mediators via the suppression of extracellular signal-regulated kinase (ERK) pathway activation. Conclusion: The results of the present study clearly suggest that BV inhibits MSU-induced inflammation in vitro, suggesting a possible role for BV in gout treatment.