• Food Science and Biotechnology
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• v.14 no.1
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• pp.147-151
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• 2005

Purified compound with intestinal immune system-modulating properties, GWE-2c, was isolated from methanol extract of Gelidium amansii by sequential procedures with silica gel column, LH-20 Sephadex gel column, and thin-layer chromatographies. In the presence of GWE-2c, strong immunoactivity in Peyers patch cell-mediated bone marrow cells was observed in vitro. In vivo intestinal immune-modulating activity was also enhanced by crude phenolic compound (GWE) of G. amansii in a dose-dependent manner. Investigation of production of several cytokines in Peyer's patch cells upon stimulation with GWE in vivo revealed the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-6 increased. Results suggest that the phenolic compound from G. amansii represents immunopotentiator and biological response modifier at in vitro and in vivo levels.

• International Journal of Oral Biology
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• v.30 no.4
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• pp.135-141
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• 2005

Although it has been known that TGF-${\beta}1$ acts as a crucial cofactor in osteoclast differentiation, its mode of action is still unclear. In the present study, we studied the effect of TGF-${\beta}1$ on the differentiation of osteoclast depending on the developmental stages. Murine bone marrow cells were induced to differentiate into mature osteoclasts in the presence of receptor activator of NF-${\kappa}B$ ligand (RANKL) and macrophage colony stimulating factor (M-CSF). In the early stage of the differentiation TRAP(-) mononuclear precursor cells were obtained from nonadherent M-CSF dependent bone marrow cells, which further differentiated into mature osteoclasts. TGF-${\beta}1$ stimulated osteoclast differentiation, which was stronger when cells were stimulated by TGF-${\beta}1$ in the early stage than the later differentiation. TGF-${\beta}1$ increased the expression of RANK and synergistically stimulated RANKL-induced activation of NF-${\kappa}B$ MAP kinase in TRAP(-) mononuclear precursor cells. These results suggest that activation of osteoclast differentiation by TGF-${\beta}1$ may be ascribed to the both increased expression and activation of RANK in the osteoclast differentiation, especially in the early stage of differentiation.

• Biotechnology and Bioprocess Engineering:BBE
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• v.8 no.3
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• pp.187-191
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• 2003

Proteolytic enzymes existing in plant cell cultured media are the major reason for the loss of secreted human granulocyte-macrophage colony-stimulating factor (hGM-CSF). The addition of pepstatin, aprotinin and PMSF relatively decreased the proteolytic degradation of hGM-CSF in a conditioned medium, but sufficient prevention against the proteolytic activity could not be obtained with chemical protease inhibitors. Gelatin, as a competitive substrate for protease, showed a stabilizing effect in a conditioned medium. Compared to the initial hGM-CSF concentration in a conditioned medium. with 10 g/L of gelatin, 68% of the hGM-CSF remained after 5 days. In a cell culture experiment, 5 g/L of gelatin significantly stimulated the hGM-CSF production and accumulation in culture media, with no growth inhibition. compared to the controls (4.72 $\mu\textrm{g}$/L), the extracellular hGM-CSF level could be increased to 39.78 $\mu\textrm{g}$/L with the addition of 5 g/L of gelatin.

• Clinical and Experimental Pediatrics
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• v.46 no.3
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• pp.271-276
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• 2003

Purpose : Granulocyte-colony stimulating factor(G-CSF) and granulocyte macrophage-colony stimulating factor(GM-CSF) are principal cytokines in granulopoiesis and their physiologic effects are mediated through binding to specific cell surface receptors. Although it is known that the level of serum G-CSF and GM-CSF, and presentation of the receptors are increased in infectious diseases, there have been no studies to find the correlation between the granulopoiesis and leukocytosis. This study was designed to measure G-CSF and GM-CSF in leukocytosis and in control and to demonstrate the possible pathogenesis of granulopoiesis in leukocytosis using quantitative analysis of G-CSF, GM-CSF and their CSFr. Methods : The plasma levels of G-CSF, GM-CSF of 13 children without leukocytosis and 14 children with leukocytosis were measured. Counts of cell surface G-CSFr and GM-CSFr were measured by combining anti G-CSFr and anti GM-CSFr monoclonal antibodies to their respective receptors by using quantitative flow cytometric assay. Results : There was no significant difference betweeen the plasma concentration of G-CSF and GM-CSF in acute leukocytosis and in the control group. However, levels of G-CSFr in acute leukocytosis decreased significantly compared to the control(P=0.012) and the levels of GM-CSFr in both groups revealed no significant difference. Conclusion : Increase in the number of leukocyte in leukocytosis was mediated by increasing the number of neutrophil, and increased plasma concentration of G-CSF may be the cause of neutrophilia. But GM-CSF did not have any influence on leukocytosis.

• Journal of Microbiology
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• v.37 no.2
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• pp.111-116
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• 1999

Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) is known to act as a signal transducer that connects TNFR2 to its downstream effector functions such as proliferation of thymocytes, regulation of gene expression, and cell death. TRAF2 consists of largely two domains, the N-terminal half that contains a signal-emanating region and the C-terminal half that is responsible for binding to the intracellular region of TNFR2. In this study, we examined the possible roles of TRAF2 in granulocyte-macrophage colony-stimulating factor (GM-CSF) gene expression and cell death. A truncated mutant of TRAF2 ( 2-263) that contains only a C-terminal half was generated, and transiently transfected to the A549 cell, a human lung cancer cell line, and L929 cell, a murine TNF-sensitive cell line. GM-CSF mRNA was induced in untransfected A540 cells both in dose- and time-dependent manner upon the exposure of TNF. However, neither the full length TRAF2 nor the mutant altered GM-CSF mRNA production regardless of the presence or absence of TNF. Furthermore, neither TRAF2 versions significantly changed the cytotoxic effect of TNF on L929 cells. These data suggest that TRAF2 may not be involved in the signal transduction pathway for GM-CSF gene induction and cell death mediated by TNF.

• The Journal of Internal Korean Medicine
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• v.27 no.4
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• pp.864-878
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• 2006

Purpose : Panax ginseng(PG) is considered to have salutary effects and stimulant actions on physical capacity. However, the effects of PG on the inflammatory cytokine secretion and hypoxia condition are still not understood. This study wasto elucidate the effect of PG on inflammatory cytokine secretion such as interleukin (IL)-1, IL-6, granulocyte macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor $(TNF)-{\alpha}$. Also, the effects on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF-1) were measured. Methods : The water extract of PG was administrated to HMC-1 cells before phorbol myristate acetate (PMA)+A23187 treatment. $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, GM-CSF, and VEGF secretion were measured by a modified enzyme-linked immunosorbent assay (ELISA). HIF-1 activation was measured by transcription factor enzyme-linked immunoassay (TF-EIA) Results : PG significantly decreased secretion of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$, and GM-CSF in PMA+A23187-induced HMC-1 cells. VEGF secretion was not changed but HIF-1 activation was decreased by the treatment of PG. Conclusions : PG inhibited the secretion of inflammatory cytokines, which impliesPG might contribute to treatment of mast cell-mediated inflammatory disease. Also, PG inhibited PMA+A23187-induced $HIF -1{\alpha}activation}$ and DNA-binding activity for HIF-1. Therefore, these data demonstrate that PG modulates inflammatory cytokines through inhibition of $HIF-1{\alpha}activation}$ activation.

• Journal of Yeungnam Medical Science
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• v.27 no.1
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• pp.57-62
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• 2010

Pulmonary alveolar proteinosis (PAP) is a rare disorder that's characterized by accumulation of surfactant components in the alveolar space. Idiopathic PAP is recognized as an autoimmune disease that's due to impaired alveolar macrophage function and this caused by autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF). We report here a case of pulmonary alveolar proteinosis that was deemed interstitial lung disease at the initial diagnosis. A 61-year-old man presented with intermittent blood tinged sputum and dyspnea on exertion. The man was a painter for 30 years and he had a 10 pack-years smoking history. Chest computerized tomography (CT) revealed multifocal ground-glass opacity with interstitial thickening at both lungs. His pulmonary function tests and methacholine test revealed non specific results. He was diagnosed with interstitial lung disease on the basis of the chest CT finding and occupational history. However, seven months later, his symptoms progressed. Follow-up chest CT was performed. Wedge resection via video-assisted thoracoscopic surgery (the anterior basal segment of the left lower lobe) was done. Microscopic examination showed large groups of alveoli with excessive amounts of surfactant and a complex mixture of protein and lipid (fat) molecules. Finally, he was diagnosed as having pulmonary alveolar proteinosis.

• Molecules and Cells
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• v.39 no.10
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• pp.734-741
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• 2016

Granulocyte-macrophage colony stimulating factor (GM-CSF) has a role in inducing emergency hematopoiesis upon exposure to inflammatory stimuli. Although GM-CSF generated murine bone marrow derived cells have been widely used as macrophages or dendritic cells in research, the exact characteristics of each cell population have not yet been defined. Here we discriminated GM-CSF grown bone marrow derived macrophages (GM-BMMs) from dendritic cells (GM-BMDCs) in several criteria. After C57BL/6J mice bone marrow cell culture for 7 days with GM-CSF supplementation, two main populations were observed in the attached cells based on MHCII and F4/80 marker expressions. GM-BMMs had $MHCII^{low}F4/80^{high}$ as well as $CD11c^+CD11b^{high}CD80^-CD64^+MerTK^+$ phenotypes. In contrast, GM-BMDCs had $MHCII^{high}F4/80^{low}$ and $CD11c^{high}CD8{\alpha}^-CD11b^+CD80^+CD64^-MerTK^{low}$ phenotypes. Interestingly, the GM-BMM population increased but GM-BMDCs decreased in a GM-CSF dose-dependent manner. Functionally, GM-BMMs showed extremely high phagocytic abilities and produced higher IL-10 upon LPS stimulation. GM-BMDCs, however, could not phagocytose as well, but were efficient at producing $TNF{\alpha}$, $IL-1{\beta}$, IL-12p70 and IL-6 as well as inducing T cell proliferation. Finally, whole transcriptome analysis revealed that GM-BMMs and GM-BMDCs are overlap with in vivo resident macrophages and dendritic cells, respectively. Taken together, our study shows the heterogeneicity of GM-CSF derived cell populations, and specifically characterizes GM-CSF derived macrophages compared to dendritic cells.

• Journal of Oral Medicine and Pain
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• v.31 no.1
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• pp.17-25
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• 2006

The present study was undertaken to determine the possible cellular mechanism of action of angiopoietin-2 in bone metabolism. The effects on the osteoblasts were determined by measuring 1) cell viability, 2) alkaline phosphatase (ALP) activity, 3) gelatinase activity, and 4) nitric oxide production. The effects on the osteoclasts were investigated by measuring 1) tartrate-resistant acid phosphatase (TRAP)(+) multinucleated cells (MNCs) formation, and 2) resorption areas after culturing osteoclast precursors. Angiopoietin-2 treatment showed a significant increase in both the viability and ALP activity of osteoblasts. Angiopoietin-2 increased the activity of gelatinase and nitric oxide production. In addition, angiopoietin-2 decreased the osteoclast generation induced by macrophage-colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL), and inhibited osteoclastic activity in (M-CSF)-dependent bone marrow macrophage (MDBM) cell cultures. Taken these results, angiopoietin-2 may be a regulatory protein within the bone marrow microenvironment.

• Advances in Traditional Medicine
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• v.6 no.3
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• pp.237-244
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• 2006

Samultang has been believed for prevention and remedy various blood diseases such as menstrual irregularity, anemia, and metrorrhagia. However, the mechanism that accounts for anti-inflammatory effects of the Samultang is still not fully understood. This study was designed to evaluate whether and how the Samultang could modulate the production of pro-inflammatory cytokines in phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187 treated-human mast cell line, HMC-1. Samultang inhibited the production of tumor necrosis factor $(TNF)-\alpha$, interleukin (IL)-6, granulocyte macrophage colony stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) in HMC-1. Maximal inhibition rate of $TNF-\alpha$, IL-6, GM-CSF, and VEGF by 0.1 mg/ml Samultang was about $70.73{\pm}3.0%,\;51.49{\pm}4.14%,\;54.03{\pm}2.09%$, and $47.95{\pm}7.86%$, respectively. Samultang partially blocked PMA plus A23187-induced cyclooxygenase (COX)-2 expression. In addition, Samultang inhibited activation of nuclear factor (NF)-kB, and extracellular signal-regulated kinase (ERK) activation. These results suggest that anti-inflammatory effect of Samulatng may be mediated by the suppression of cytokine production and COX-2 activation via down-regulation of NF-kB and ERK activation.