• Journal of Life Science
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• v.27 no.11
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• pp.1256-1261
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• 2017

${\beta}$-glucan is a constituent of the cell wall of fungi, yeast and plants. It plays an important role in the immune system such as activation of immunocyte, release of pro-inflammatory and anti-cancer effect. The immune system maintains a healthy immune homeostasis. However, when pathogenic substances enter the body, immune homeostasis can break down and disease can be triggered. Therefore, we studied a substance that regulates immune homeostasis. The purpose of the study we demonstrated whether the ${\beta}$-glucan can be applied to the immune-modulation effects in human monocytic THP-1 cells. ${\beta}$-glucan was incubated in THP-1 cells at various concentrations. The $TNF-{\alpha}$ mRNA expression and protein levels were analyzed by ELISA and Real-time PCR. Additionally, the expression of MAPKs (p38 and JNK), $I{\kappa}B-{\alpha}$ and $NF-{\kappa}B$ p50 were analyzed by western blot. ${\beta}$-glucan enhanced the production of $TNF-{\alpha}$ mRNA expression and protein levels in human monocytic THP-1 cells. In addition, activation of MAPKs (p38 and JNK) and $NF-{\kappa}B$ p50 induced by ${\beta}$-glucan were increased. The study suggests that ${\beta}$-glucan contributes to immune-stimulation effect by production $TNF-{\alpha}$ in human monocytic THP-1 cells, and that MAPKs and $NF-{\kappa}B$ p50 are involved in the process. Synthetically, we have suggested ${\beta}$-glucan may be improved to immune system effect in human monocytic THP-1 cells.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.75-75
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• 2003

We report upon the cytotoxic activity of the ginseng saponin metabolite, Compound K (20-O-D-glucopyranosyl-20(S)-protopanaxadiol, IH90l) on various human leukemia cell lines. Compound K had most effect on U937, a human monocytic leukemia cell line, which on treatment showed; a exposure of phosphatidylserine from the inner cell membrane to the outer cell membrane, the formation of apoptotic bodies and DNA fragmentation, - characteristics of apoptosis. Compound K induced apoptosis by up-regulating Bax, disrupting the mitochondria membrane potential, and by activating caspase 9 and caspase 3. Therefore, we suggest that Compound K inhibit U937 cell growth by inducing apoptosis through the up-regulation of Bax and caspase activation.

• YAKHAK HOEJI
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• v.52 no.2
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• pp.111-116
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• 2008

Diethylstilbestrol (DESB) is a synthetic estrogen not only that routinely prescribed, but also that known to be a teratogen. In this study, we found a novel pharmacological feature that DESB is able to positively modulate CD29 $({\beta}1-integrin)$ function. Thus, DESB up-regulated homotypic cell-cell adhesion of monocytic U937 cells mediated by CD29. However, DESB did not increase the surface level of CD29 and its binding activity to ligand (fibronectin), according to flow cytometric analysis and cell-fibronectin adhesion assay. Instead, the DESB-mediated up-regulation of cell-cell adhesion was blocked by several signaling enzyme inhibitors. Treatment of U0126 [an extracellular signal-regulated kinase (ERK) inhibitor], SB20358 (a p38 inhibitor) or Rp-8-pCPT-cGMP (a protein kinase G inhibitor) clearly inhibited DESB-mediated up-regulation of cell-cell adhesion induced by CD29. However, estrogen receptor antagonist ICI 182,780 failed to abrogate DESB effect. Therefore, our data suggest that DESB may up-regulate CD29-mediated cell-cell adhesion via modulating intracellular signaling enzymes such as ERK, PKG, and p38, independent of estrogen receptor function.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.515-523
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• 2016

Adhesion events of monocytes represent an important step in inflammatory responses induced by chemokines. The ${\beta}1$-integrin CD29 is a major adhesion molecule regulating leukocyte migration and extravasation. Although several adhesion molecules have been known as regulators of CD29, the molecular interactions between CD29 and its regulatory adhesion molecules (such as CD98 and CD147) have not been fully elucidated. Therefore, in this study, we examined whether these molecules are functionally, biochemically, and cell-biologically associated using monocytic U937 cells treated with aggregation-stimulating and blocking antibodies, as well as enzyme inhibitors. The surface levels of CD29, CD98, and CD147 (but not CD43, CD44, and CD82) were increased. The activation of CD29, CD98, and CD147 by ligation of them with aggregation-activating antibodies triggered the induction of cell-cell adhesion, and sensitivity to various enzyme inhibitors and aggregation-blocking antibodies was similar for CD29-, CD98-, and CD147-induced U937 cell aggregation. Molecular association between these molecules and the actin cytoskeleton was confirmed by confocal microscopy and immunoprecipitation. These results strongly suggest that CD29 might be modulated by its biochemical and cellular regulators, including CD98 and CD147, via the actin cytoskeleton.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.134.2-135
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• 2003

We examined the minimal amino acid sequence of bovine lactoferricin (Lfcin-B), a cationic peptide corresponding to residues 17-41 near the N-terminus of bovine lactoferrin, to induce apoptosis in THP-l human monocytic leukemic cells using synthetic peptides. A synthetic peptide (Lfc-17/29, amino acid sequence; FKCRRWQWRMKKL) which is consist of 13 amino acids near the N-terminus of Lfcin-B induced cell death in THP-1 cells in a dose-dependent manner, showing apparent apoptotic changes such as hypodiploid forms of genomic DNA and apoptotic DNA fragmentation. (omitted)

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.166.3-167
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• 2003

Helenalin, a cell-permeable pseudoguainolide sesquiterpene lactone, is a potent anti-inflammatory agent that inhibits $NF-{\kappa}B$ DNA binding activity by selectively alkylating the p65 subunit of $NF-{\kappa}B$. Transcription factors such as $NF-{\kappa}B$ provide powerful target of drugs to use in the treatment of cancer. Human promyelocytic leukemia HL-60 cells are differentiated into monocytic or granulocytic lineage when treated with 1,25-dihydroxyvitamin $D_3{\;}[1,25-(OH)_2D_3]$ or all-trans-retinoic acid (ATRA), respectively. (omitted)

• Biomedical Science Letters
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• v.24 no.2
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• pp.134-137
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• 2018

S100A8 and S100A9 are involved in pathogenesis of cancer by induction or inhibition of cancer as well as inflammation. In this study, we investigated the association of S100A8 and S100A9 with pathogenesis of leukemia using human monocytic leukemia cells, THP-1. The expression of TLR4, which is a known receptor of S100A8 and S100A9, was examined by using flow cytometry and Western blotting. THP-1 cells have high surface and cytosol expression of TLR4. S100A8 and S100A9 suppressed the cell survival, and this suppression was found to be associated with apoptosis because they increased the number of apoptotic cells in a dose- and a time-dependent manners. However, S100A8 and S100A9 had no effect on the survival and apoptosis of monocytes isolated from the peripheral blood. We next examined the apoptotic effect of lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA), which are other ligands of TLR4, in THP-1 cells. Lipopolysaccharide had no effect on cell survival, but MPLA is effective on the cell apoptosis. These results suggest that S100A8 and S100A9 may regulate leukemia cell survival via TLR4, which is an essential receptor in the pro-apoptotic mechanism induced by S100A8 and S100A9. These findings may shed light on development of a possible therapeutic drug for leukemia treatment.

• The Journal of the Korean Society for Microbiology
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• v.35 no.2
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• pp.149-157
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• 2000

Mycobacterium tuberculosis is capable of growing and survival within macrophage. The purpose of this study was to identify the genes regulated by infection of mycobacteria in human monocytic THP-1 cells. We used the differential display reverse transcriptase polymerase chain reaction (DD RT-PCR) and nothern blot analysis to confirm the differentially expressed genes from THP-1 cells infected with live Mycobacterium tuberculosis H37Rv, heat-killed Mycobacterium tuberculosis H37Rv and live Mycobacterium bovis BCG. Among many up or down-regulated clones, 27 clones were sequenced and compared with known genes on GenBank. Thirteen of over-expressed clones from THP-1 cells infected with live Mycobacterium tuberculosis H37Rv were identical to human prothymosin alpha, eight were novel clones and six clones showed homology with Human ferritin H chain, Esherichia coli bgl, Mouse RNA-dependent EIF-2 alpha kinase, E. coli htrL, Hyaluronan receptor and T cell receptor. Our result suggests that Mycobacterium tuberculosis might regulate prothymosin alpha gene transcription in monocytic THP-1 cell.

• 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.

• Journal of Life Science
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• v.22 no.12
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• pp.1637-1643
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• 2012

This study investigated the effects of PG on IL-$1{\beta}$ expression and determined cellular factors involved in PG-mediated IL-$1{\beta}$ up-regulation in mononuclear cells in order to understand the molecular mechanisms underlying inflammatory responses associated with bacterial pathogen-associated molecular patterns in the diseased artery. Exposure of human monocytic leukemia THP-1 cells to PG resulted in enhanced secretion of IL-$1{\beta}$ and also profound induction of the IL-$1{\beta}$ gene transcript. These effects were abrogated by OxPAPC, an inhibitor of TLR-2/4. Pharmacological inhibitors such as U0126, SP6001250, Akti IV, rapamycin, and DPI also significantly attenuated PG-mediated IL-$1{\beta}$ up-regulation. However, polymyxin B did not influence the IL-$1{\beta}$ expression. This study indicates that PG contributes to vascular inflammation in atherosclerotic plaques by up-regulating expression of IL-$1{\beta}$ via TLR-2, Akt, mTOR, MAPKs, and ROS.