• YAKHAK HOEJI
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• v.51 no.6
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• pp.482-489
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• 2007

Kaempferitrin, isolated from Kenaf (Hibiscus cannabinus), was examined to evaluate its modulatory effects on antigen-presenting cell functions of macrophages/monocytes such as phagocytosis of foreign materials, up-regulation of costimulatory molecules (CD40, CD80 and CD86), adhesion molecule activation, and antigen processing and presentation. Kaempferitrin strongly blocked up-regulation of CD40, CD80 and CD86, but not pattern recognition receptor (PRR) (e.g., TLR2). It also suppressed functional activation of CD29 (${\beta}1$-integrins), as assessed by cell-cell adhesion assay, required for T cell-antigen-presenting cell (APC) interaction. Furthermore, this compound did not block a simple activation of CD29, as assessed by cell-fibronectin adhesion assay. However, the compound did not diminish phagocytic uptake, an initial step for antigen processing, and ROS generation in RAW264.7 cells. In particular, to understand molecular mechanism of kaempferitrin-mediated inhibition, the regulatory role of LPS-induced signaling events was examined using immunoblotting analysis. Interestingly, this compound dose dependently suppressed the phosphorylation of $I{\kappa}B{\alpha}$, Src, Akt and Syk, demonstrating that it can negatively modulate the activation of these signaling enzymes. Therefore, our data suggested that kaempferitrin may be involved in regulating APC function-relevant immune responses of macrophages and monocytes by regulating intracellular signaling.

• Journal of Life Science
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• v.27 no.2
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• pp.217-224
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• 2017

Carbon monoxide (CO), a reaction product of cytoprotective enzyme heme oxygenase-1 (HO-1), is a gaseous messenger with anti-proliferative, anti-apoptotic, and anti-inflammatory actions in many cell types. Here, we investigated the role of CO on the process of monocyte differentiation induced by phorbol 12-myristate 13-acetate (PMA) in human monocytic THP-1 cells. CORM-2 (tricarbonyldichlororuthenium (II) dimer, $Ru2Cl_4(CO)_6$), a CO-releasing compound, decreased a marked cell adherence with a slight reduction of proliferation in monocytic THP-1 cells treated with PMA. And, CORM-2 significantly inhibited expression of differentiation markers such as CD14, CD11b plus CD18 (macrophage-1 antigen, Mac-1 or complement receptor 3, CR3) and phagocytosis of carboxylate-modified red fluorescent latex beads, in PMA-stimulated THP-1 cells. For the further experiments, differentiation of PMA-treated cells was enhanced after the initial 2 days stimulus by removing the PMA-containing media then incubating the cells in fresh media for a another 4 days. And, we observed the secretion of inflammatory cytokines and phagocytosis in differentiated macrophages. Treatment with CORM-2 significantly abolished the secretion of IL-6, $TNF-{\alpha}$ and phagocytosis using fluorescence-conjugated E. coli (K-12 strain) bioparticles in lipopolysaccharide (LPS)-stimulated differentiated macrophages. In conclusion, these results suggest that CO inhibits the differentiation of monocytic THP-1 cells as well as the activation of differentiated macrophages.

• BMB Reports
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• v.39 no.6
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• pp.722-729
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• 2006

Recently, we have reported that 3-hydrogenkwadaphnin (3-HK), a diterpene ester isolated from Dendrostellera lessertii (Thymealeaceae), is very effective against leukemia cell lines without any detectable effects on normal cells (Moosavi et al., 2005b). In this study, we report that 3-HK induces $G_1$ cell-cycle arrest, differentiation and apoptosis in APL NB4 cell line. Indeed, the drug between 24 to 96 h induced 7-65% growth inhibition of NB4 cells. Cell viability was also decreased by 2-55% between 24 to 96 h treatments with the drug, respectively. These effects of the drug were also dose-dependent. According to flow cytomtry results, 3-HK (15 nM) induced a significant G1-arrest up to 24 h which was consequently followed with appearance of sub-$G_1$ peak at 72 to 96 h. Hoechst 33258 staining and DNA fragmentation assays confirmed the occurrence of apoptosis among the treated cells. On the other hand, NBT reducing assay, Wright-Giemsa staining, phagocytic activity and expression of cell surface markers (CD11b and CD14) confirmed that the inhibition of proliferation is associated with differentiation especially toward macrophage-like morphology. Interestingly, 3-HK at 5 and 10 nM enhanced the effects of all-trans retinoic acid (ATRA) in NB4 cells. Based on these results, 3-HK might become an ideal candidate for treatment of APL patients pending full exploration of its biological functions.

• Food Science and Biotechnology
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• v.16 no.5
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• pp.796-801
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• 2007

This study was conducted to investigate antioxidant activity and anti-immunological inflammatory effect of Allium victorialis subsp. platyphyllum extracts (AVPEs). Antioxidant activities of AVPEs were determined by free radical scavenging assay and reducing power test. Leaf-part extract had comparatively better antioxidant activity than other-part extracts. Antioxidant activity of extracts had protective effect for human umbilical vein endothelial cells (HUVECs) against superoxide anions secreted from activated neutrophils. Also, we observed AVPEs had inhibitory effects on the adherence of monocytic THP-1 to HUVEC monolayer to the basal level. Inhibitory effect on cell adhesion was caused by suppression of tumor necrosis factor-${\alpha}\;(TNF-{\alpha})-upregulated$ expression of vascular cellular adhesion molecule-1 (VCAM-1) and E-selectin in HUVECs. From these results, we expect to support the evidence of anti-immunological inflammatory effects of Allium victorialis subsp. platyphyllum (AVP) as a Korean traditional pharmaceutical.

• BMB Reports
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• v.37 no.4
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• pp.507-514
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• 2004

Gamma irradiation ($\gamma$-IR) is reported to have diverse effects on immune cell apoptosis, survival and differentiation. In the present study, the immunomodulatory effect of a low dose $\gamma$-IR (5~10 Gy) was investigated, focusing on the role of NF-${\kappa}B$ in the induction of the B cell differentiation molecule, CD23/FceRII. In the human B cell line Ramos, $\gamma$-IR not only induced CD23 expression, but also augmented the IL-4-induced surface CD23 levels. While $\gamma$-IR did not cause STAT6 activation in these cells, it did induce both DNA binding and the transcriptional activity of NF-${\kappa}B$ in the $I{\kappa}B$ degradation-dependent manner. It was subsequently found that different NF-${\kappa}B$ regulating signals modulated the $\gamma$-IR-or IL-4-induced CD23 expression. Inhibitors of NF-${\kappa}B$ activation, such as PDTC and MG132, suppressed the $\gamma$-IR-mediated CD23 expression. In contrast, Ras, which potentiates $\gamma$-IR-induced NF-${\kappa}B$ activity in these cells, further augmented the $\gamma$-IR- or IL-4-induced CD23 levels, The induction of NF-${\kappa}B$ activation and the subsequent up-regulation of CD23 expression by $\gamma$-IR were also observed in monocytic cells. These results suggest that $\gamma$-IR, at specific dosages, can modulate immune cell differentiation through the activation of NF-${\kappa}B$, and this potentially affects the immune inflammatory response that is mediated by cytokines.

• Journal of Microbiology and Biotechnology
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• v.16 no.10
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• pp.1544-1553
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• 2006

The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/ml$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited cell adhesion that non-activated U937 monocytic cell adhesion to HUVECs activated with $IL-1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with $IL-1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to $IL-1{\beta}$-stimulated HUVECs was completely suppressed by 121% at a concentration of $18.5{\mu}g/ml$. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin, and VE-cadherin to NF-kB, based on western bolt analysis. It also inhibited IL-l-stimulated HUVEC expression of the adhesion molecules, ICAM-l by 40%, VCAM-l by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities, and non-toxicity may be expected from these results.

• 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.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2145-2148
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• 2012

Objective: This study concerns expression of PBK/TOPK during differentiation of HL-60 leukemic cells induced by tetradecanoyl phorbol acetate (TPA). Methods: Wright-Giemsa staining was performed to observe morphological changes in the HL-60 cells, and flow cytometry was used to assess the cell cycle and CD11b, CD14, CD13, and CD33 expression. PBK/TOPK levels were determined by Western blot analysis. Results: After treating HL60 cells with $5.1{\times}10^{-9}$ mmol/L of TPA for three days, the number of nitroblue-tetrazolium-positive cells and CD11b, CD13, and CD14 expression increased, whereas the PBK/TOPK levels decreased. Conclusions: TPA can inhibit proliferation and induce differentiation of HL60 cells of the granulocytic or monocytic lineage. PBK/TOPK expression was downregulated during this process, whereas the Pho-PBK/TOPK expression was increased.

• Journal of Marine Bioscience and Biotechnology
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• v.1 no.3
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• pp.156-162
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• 2006

The halophilic enterobacteria, Enterobacteria cancerogenus, was isolated from the intestines of the fusiform fish (Trachurus japonicus) to yield a protein-like material termed PLM-f74. PLM-f74 was characterized by strong inhibition ratios to angiogenesis (82.8% at the concentration of $18.5{\mu}g/mL$) and elevated antioxidative capacities with low toxicity. The PLM-f74 is a glycoprotein comprised of saccharides and amino acids. PLM-f74 inhibited non-activated U937 monocytic cell adhesion to HUVECs activated with IL-$1{\beta}$ by 78.0%, and the adherence of U937 cells treated with the PLM-f74 and stimulated with IL-$1{\beta}$ to unstimulated HUVECs decreased by 102%. When both cell types were pretreated with PLM-f74, the adhesion of U937 cells to IL-$1{\beta}$ stimulated HUVECs was completely suppressed by 121% at a concentration of 18.5 ug/mL. PLM-f74 blocked signal pathways from VEGFR2, PI3K, ${\beta}$-catenin and VE-cadherin to NF-kB based on western bolt analysis. And also inhibited IL-1-stimulated HUVEC expression of the adhesion molecules, ICAM-1 by 40%, VCAM-1 by 60%, and E-selectin by 70% at the same concentration noted above. New anti-angiogenic and anti-cell adhesion materials showing elevated antioxidative capacities and non-toxicity may be expected from these results.

• Journal of Life Science
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• v.34 no.4
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• pp.271-278
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• 2024

Redox factor (Ref)-1, a ubiquitously expressed protein, acts as a modulator of redox-sensitive tran- scription factors and as an endonuclease in the repair pathway of damaged DNA. However, the function of Ref-1 in the differentiation of monocytes into macrophages has not been defined. In this study, we investigated the effects of Ref-1 on the monocyte differentiation process using the human monocytic cell line THP-1. The differentiation agent PMA increased cell adhesion over time and showed a sig- nificant increase in phagocytic function but decreased the intracellular amount of Ref-1. Ref-1 inhibitor E3330 and Ref-1 knockdown using the siRNA technique reduced cell adhesion and the expression of differentiation markers, such as CD14, ICAM-1, and CD11b, by PMA stimulation. This means that the role of Ref-1 is absolutely necessary in the initial process of differentiating THP-1 cells stimulated by PMA. Next, the distribution of Ref-1 was examined in the cytoplasm and nucleus of THP-1 cells stimulated with PMA. Surprisingly, PMA stimulation resulted in the rapid translocation of Ref-1 to the nucleus. To prove that movement of Ref-1 to the nucleus is required for monocyte differentiation, a Ref-1 vector with the nuclear localization sequence (NLS) deleted was used. As a result, overexpression of ∆NLS Ref-1, which restricted movement to the nucleus, suppressed the expression of differentiation markers and notably reduced phagocytic function in PMA-stimulated THP-1 cells. In conclusion, these data suggest that the differentiation of monocytic THP-1 cells requires Ref-1 nuclear translocation during the initial process of biochemical events following stimulation from PMA.