• Journal of Ginseng Research
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• v.37 no.4
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• pp.389-400
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• 2013

Korean Red Ginseng (KRG) has been reported to exert anticancer, anti-oxidant, and anti-inflammatory effects. However, there has been no report on the effect of KRG on skin pigmentation. In this study, we investigated the inhibitory effect of KRG on melanocyte proliferation. KRG extract (KRGE) at different concentrations had no effect on melanin synthesis in melan-A melanocytes. Saponin of KRG (SKRG) inhibited melanin content to 80% of the control at 100 ppm. Keratinocyte-derived factors induced by UV-irradiation were reported to stimulate melanogenesis, differentiation, proliferation, and dendrite formation. In this study, treatment of melan-A melanocytes with conditioned media from UV-irradiated SP-1 keratinocytes increased melanocyte proliferation. When UV-irradiated SP-1 keratinocytes were treated with KRGE or SKRG, the increase of melanocyte proliferation by the conditioned media was blocked. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was produced and released from UV-irradiated keratinocytes. This factor has been reported to be involved in regulating the proliferation and differentiation of epidermal melanocytes. In this study, GM-CSF was significantly increased in SP-1 keratinocytes by UVB irradiation ($30mJ/cm^2$), and the proliferation of melan-A melanocytes increased significantly by GM-CSF treatment. In addition, the proliferative effect of keratinocyte-conditioned media on melan-A melanocytes was blocked by anti-GM-CSF treatment. KRGE or SKRG treatment decreased the expression of GM-CSF in SP-1 keratinocytes induced by UVB irradiation. These results demonstrate that UV irradiation induced GM-CSF expression in keratinocytes and KRGE or SKRG inhibited its expression. Therefore, KRG could be a good candidate for regulating UV-induced melanocyte proliferation.

• YAKHAK HOEJI
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• v.35 no.2
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• pp.135-141
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• 1991

The general pharmacological tests with rhGM-CSF indicated that it had no influences on rotarod and locomotor activity tests, but shortened hexobarbital-sleeping time at the large dose of 3 mg/kg s.c. in mice. It elicited no hypothermic, analgesic and antiepileptic action. No influences on blood pressure and respiration in rabbits were observed at the dose of 1 mg/kg, i.v. and it did neither affect the receptors of adrenaline, acetylcholine, serotonin, histamine, kinin and oxytocin, nor antagonize the actions of histamine, serotonin and oxytocin at its concentrations of 1$\times$$10^{-6}$g/ml. However, this substance was demonstrated to stimulate the formation of leucocytes in rats.

• 한국생물공학회:학술대회논문집
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• 2002.04a
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• pp.321-324
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• 2002

In situ recovery of recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) was performed in transgenic Nicotiana tabacum cell suspension cultures. Aqueous two-phase systems (ATPS) were used to utilize its biocompatibility. Transgenic plant cells could be grown up to 15.7 g/L in normal medium and 18.6 g/L in ATPS composed of 6% (w/w) polyethylene glycol (PEG) 20,000 and 10% (w/w) dextran 2,000,000. It was proved that the A TPS was not harmful to cell growth. In addition, It is expected to recover hGM-CSF simultaneously with cell growth. Using this method, maximum hGM-CSF concentration at 1.64 ng/mL was obtained on day 3.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.4
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• pp.586-591
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• 2010

Chemokine and Growth Factor are major mediumtors of immuno-inflammatory pathway. The purpose of this study is to investigate whether productions of Chemokine and Growth Factor in lipopolysaccharide (LPS)-induced mouse macrophage RAW 264.7 cells are modulated by Gallic acid (GA), which is easily founded in tannin-containing natural materials such as red wine, green tea, grape juice, and Corni Fructus. Productions of Chemokine and Growth Factor were analyzed by High-throughput Multiplex Bead based Assay with Bio-plex Suspension Array System based on $xMAP^{(R)}$ (multi-analyte profiling beads) technology. At first, cell culture supernatant was obtained after treatment with LPS and GA for 24 hour. Then, the antibody-conjugated beads were added and incubated for 30 minutes. After incubation, detection antibody was added and incubated for 30 minutes. And Strepavidin-conjugated Phycoerythrin (SAPE) was added. After incubation for 30 minutes, the level of SAPE fluorescence was analyzed on Bio-plex Suspension Array System. Based on fluorescence intensity, concentrations of Chemokine and Growth Factor were determined. The results of the experiment are as follows. GA significantly inhibited the production of interferon-inducible protein (IP)-10, keratinocyte-derived chemokine(KC), and vascular endothelial growth factor (VEGF) in LPS-induced RAW 264.7 cells at the concentration of 25, 50, 100, 200 uM (p<0.05). GA significantly inhibited the production of monocyte chemoattractant protein-1(MCP-1) and macrophage-colony stimulating factor(M-CSF) in LPS-induced RAW 264.7 cells at the concentration of 50, 100, 200 uM (p<0.05). GA diminished the production of granulocyte macrophage-colony stimulating factor (GM-CSF) in LPS-induced RAW 264.7 cells. But GA did not show the inhibitory effect on the production of leukemia inhibitory factor (LIP) and macrophage inflammatory protein (MIP)-2 in LPS-induced RAW 264.7 cells. These results suggest that GA has the immuno-modulating activity related with its inhibitory effects on the production of IP-10, KC, MCP-1, VEGF, and M-CSF in LPS-induced macrophages.

• 한국생물공학회:학술대회논문집
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• 2003.10a
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• pp.231-231
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• 2003

• 대한두경부종양학회:학술대회논문집
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• 1994.11a
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• pp.20-20
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• 1994

• 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.

• Biotechnology and Bioprocess Engineering:BBE
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• v.6 no.1
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• pp.72-74
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• 2001

Transgenic Nicotiana tabacum cells were cultivated for the production of murine granulocyte macrophage-colony stimulating factor (mGM-CSF) in both a stirred tank bioreactor and an airlift bioreactor with draft tube. Cell growth and mGM-CSF production in the airlift bioreactor were found to be better than those achieved in the stirred tank bioreactor. In the airlift bioreactor, 9.0g/L of cells and 2.2ng/mL of mGM-CSF were obtained (11.0g/L and 2.4ng/mL, respectively in shake flasks). Although the lag period was prolonged and mGM-CSF production was lowered by 33% in the stirred thank bioreactor as compared to the control culture, the maximum cell density was increased up to 12.0g/L due to better mixing by agitation at the higher cell density.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.330-330
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• 1994

항암화학요법후 가장 심각한 부작용의 하나는 중성구 감소에 의한 감염이다. 본원에서는 rhGM-CSF을 이용한 제 I상 임상연구에서 150-500$\mu$g/M$^2$/day가 biologically active dose임을 보고한 바 있다. 연자들은 연세암센터에 내원하여 진행성 악성종양으로 병리조직학적 진단을 받고 항암화학요법 시행후 골수억제가 예상되는 환자를 대상으로 GM-CSF 용량에 따른 안전성 및 독성을 검토하고 백혈구 감소증 및 감염의 예방, 치료효과를 분석하여 임상사용권장량을 결정하기위한 2상 연구덜 대상환자의 동의를 얻은후 시행하였다. 대상환자는 37명 (여 26, 남 11)이었고, 항암제는 Adriamycin, Cisplatin, VP-l6 이 주로 사용되었다. 최적임상사용권장량을 결정하기 위하여 1500$\mu\textrm{g}$/M$^2$/day을 12명, 250$\mu\textrm{g}$/M$^2$/day을 12명, 350$\mu\textrm{g}$/M$^2$/day을 13명의 환자에게 투여하였다. 첫번째 항암요법에는 rhGM-CSF을 투여하지않고 (비투여기) 두번째 항암요법에서는 항암요법후 익일부터 10일간 연속, 매일 1회 피하주사하여 (투여기), rhGM-CSF 투여기와 비투여기의 백혈구 감소중 정도의 차이를 비교하였다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.306-306
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• 1994

항암화학요법후 가장 심각한 부작용의 하나는 중성구 감소에 의한 감염이다. 본원에서는 rhGM-CSF을 이용한 제 I상 임상연구에서 150-500$\mu$g/M$^2$/day가 biologically active dose임을 보고한 바 있다. 연자들은 연세암센터에 내원하여 진행성 악성종양으로 병리조직학적 진단을 받고 항암화학요법시행후 골수억제가 예상되는 환자를 대상으로 GM-CSF 용량에 따른 안전성 및 독성을 검토하고 백혈구 감소증 및 감염의 예방, 치료효과를 분석하여 임상사용권장량을 결정하기위한 2상 연구를 대상환자의 동의를 얻은후 시행하였다. 대상환자는 37명 (여 26, 남 11)이었고, 항암제는 Adriamycin, Cisplatin, VP-16이 주로 사용되었다. 최적임상사용권장량을 결정하기 위하여 1500$\mu\textrm{g}$/M$^2$/day을 12명, 250$\mu\textrm{g}$/M$^2$/day을 12명, 350$\mu\textrm{g}$/M$^2$/day을 13명의 환자에게 투여하였다. 첫번째 항암 요법에는 rhGM-CSF을 투여하지않고 (비투여기) 두 번째 항암요법에서는 항암요법후 익일부터 10일간 연속, 매일 1회 피하주사하여 (투여기), rhGM-CSF 투여기와 비투여기의 백혈구 감소증 정도의 차이를 비교하였다.