• Journal of Ginseng Research
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• v.39 no.4
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• pp.322-330
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• 2015

Background: UV-irradiated keratinocytes secrete various proinflammatory cytokines. UV-induced skin damage is mediated by growth factors and proinflammatory cytokines such as granulocyte macrophage colony stimulating factor (GM-CSF). In a previous study, we found that the saponin of Korean Red Ginseng (SKRG) decreased the expression of GM-CSF in UVB-irradiated SP-1 keratinocytes. In this study, we attempted to find the inhibitory mechanism of SKRG on UVB-induced GM-CSF expression in SP-1 keratinocytes. Methods: We investigated the inhibitory mechanism of SKRG and ginsenosides from Panax ginseng on UVB-induced GM-CSF expression in SP-1 keratinocytes. Results: Treatment with SKRG decreased the expression of GM-CSF mRNA and protein induced by irradiation of UVB in SP-1 keratinocytes. The phosphorylation of ERK was induced by UVB at 10 min, and decreased with SKRG treatment in SP-1 keratinocytes. In addition, treatment with SKRG inhibited the UVB-induced phosphorylation of epidermal growth factor receptor (EGFR), which is known to be an upstream signal of ERK. From these results, we found that the inhibition of GM-CSF expression by SKRG was derived from the decreased phosphorylation of EGFR. To identify the specific compound composing SKRG, we tested fifteen kinds of ginsenosides. Among these compounds, ginsenoside-Rh3 decreased the expression of GM-CSF protein and mRNA in SP-1 keratinocytes. Conclusion: Taken together, we found that treatment with SKRG decreased the phosphorylation of EGFR and ERK in UVB-irradiated SP-1 keratinocytes and subsequently inhibited the expression of GM-CSF. Furthermore, we identified ginsenoside-Rh3 as the active saponin in Korean Red Ginseng.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.16 no.1
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• pp.365-370
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• 2015

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is an important hematopoietic growth factor and immune modulator. The aim of this study was to evaluate the effects of GM-CSF on the development and cell number of porcine parthenotes, as well as on their expression of implantation-related genes. In the present study, porcine parthenogenatic activated embryos were cultured in a protein-free culture medium in the absence or presence of 5, 10 and 20 ng/ml GM-CSF for 7 days. The percentage of blastocyst formation, total cell number and gene expressions were evaluated. The results showed that the addition of 20 ng/ml GM-CSF to protein-free culture medium significantly increased the blastocoel formation ($26.14{\pm}2.03%$ vs. $3.55{\pm}0.51%$, p < 0.05). In addition, the cell number also increased when they were cultured in the presence of 20 ng/ml GM-CSF ($43.51{\pm}3.6%$ vs. $30.68{\pm}5.51%$, p < 0.05). A real time reverse transcripts polymerase chain reaction (RT-PCR) showed that GM-CSF enhances mRNA expression of the interleukin-6, but does not influence the leukemia inhibitory factor (LIF) receptor mRNA expression in blastocyst stage parthenotes. These results suggest that GM-CSF may enhance the viability of porcine embryos developing in vitro in a defined culture medium.

• Development and Reproduction
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• v.13 no.3
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• pp.191-198
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• 2009

In an attempt to simultaneously produce two human proteins, hGH and hG-CSF, in the milk of transgenic mice, we constructed goat $\beta$-casein-directed hGH and hG-CSF expression cassettes individually and generated transgenic mice by co-injecting them into mouse zygotes. Out of 33 transgenic mice, 29 were identified as double transgenic harboring both transgenes on their genome. All analyzed double transgenic females secreted both hGH and hG-CSF in their milks. Concentrations ranged from 2.1 to $12.4\;mg/m{\ell}$ for hGH and from 0.04 to $0.13\;mg/m{\ell}$ for hG-CSF. hG-CSF level was much lower than hGH level but very similar to that of single hG-CSF mice, which were introduced with hG-CSF cassette alone. In order to address the causes of concentration difference between hGH and hG-CSF in milk, we examined mRNA level of hGH and hG-CSF in the mammary glands of double transgenic mice and tissue specificity of hG-CSF mRNA expression in both double and single transgenic mice. Likewise protein levels in milk, hGH mRNA level was much higher than hG-CSF mRNA, and hG-CSF mRNA expression was definitely specific to the mammary glands of both double and single transgenic mice. These results demonstrated that two transgenes have distinct transcriptional potentials without interaction each other in double transgenic mice although two transgenes co-integrated into same genomic sites and their expressions were directed by the same goat $\beta$-casein promoter. Therefore goat $\beta$-casein promoter is very useful for the multiple production of human proteins in the milk of transgenic animals.

• Journal of Korean Neurosurgical Society
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• v.40 no.3
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• pp.193-195
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• 2006

Hydrocephalus is usually defined as the condition of ventricular dilatation due to the overproduction of cerebrospinal fluid[CSF] or dysfunction of absorption. The pattern of the CSF circulation may change after a cranioplasty secondary to previous decompressive craniectomy for refractory intracranial hypertension after head injury. The effect of the cranioplasty on CSF hydrodynamics has not been explored exactly. We report two cases of acute hydrocephalus developed after cranioplasty and discuss about the clinical importance with review of literatures.

• Applied Microscopy
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• v.39 no.3
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• pp.253-260
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• 2009

GM-CSF is a multipotent growth factor, which also plays an important role during the process of wound healing. rrhGM-CSF was specifically produced from rice cell culture in our laboratory (Hanson Biotech Co., Ltd, Daejeon). The rrhGMCSF contains more oligosaccharide side chains than any other types of GM-CSF. This work was taken to evaluate the influence on wound healing of rrhGM-CSF in male golden hamsters. Full thickness skin defects of 9 mm in diameter were made in the back of hamsters, and 100 ${\mu}L$ ointment containing rrhGM-CSF 50 ${\mu}g/mL$ was applied. Control groups were given ointment without rrhGM-CSF. The wound sizes were relatively reduced and skin was well regenerated in the experimental group compared with the control group. Structurally, reepithelialization and architecture of the skin following injury were well accomplished in the experimental group. And also, positive reaction of PCNA of the skin following injury was more prominent in rrhGM-CSF containing ointment treatment group. Since this type of GM-CSF has highly glycosylated side chains, the effectiveness might be retain longer and stable, regarding acceleration of wound healing in the animal model. The present study has important implications for further development of the therapeutic manipulation of wound healing using rrhGM-CSF.

• Communications for Statistical Applications and Methods
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• v.14 no.3
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• pp.577-582
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• 2007

A continuum structure function (CSF) is a non-decreasing mapping from the unit hypercube to the unit interval. A B-type CSF, defined in the text, is a CSF whose behaviour is modeled by its underlying binary structures. As the measure of importance of a system component for a B-type CSF, the structural and reliability importance of a component at a system level ${\alpha}$(0 < ${\alpha}$ < 1) are defined and their properties are deduced.

• Journal of Korean Neurosurgical Society
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• v.58 no.1
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• pp.36-42
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• 2015

Objective : Complete sellar floor reconstruction is critical to avoid postoperative cerebrospinal fluid (CSF) leakage during transsphenoidal surgery. Recently, the pedicled nasoseptal flap has undergone many modifications and eventually proved to be valuable and efficient. However, using these nasoseptal flaps in all patients who undergo transsphenoidal surgery, including those who had none or only minor CSF leakage, appears to be overly invasive and time-consuming. Methods : Patients undergoing endoscopic endonasal transsphenoidal tumor surgery within a 5 year-period were reviewed. Since 2009, we classified the intraoperative CSF leakage into grades from 0 to 3. Sellar floor reconstruction was tailored to each leak grade. We did not use any tissue grafts such as abdominal fat and did not include any procedures of CSF diversions such as lumbar drainage. Results : Among 200 cases in 188 patients (147 pituitary adenoma and 41 other pathologies), intraoperative CSF leakage was observed in 27.4% of 197 cases : 14.7% Grade 1, 4.6% Grade 2a, 3.0% Grade 2b, and 5.1% Grade 3. Postoperative CSF leakage was observed in none of the cases. Septal bone buttress was used for Grade 1 to 3 leakages instead of any other foreign materials. Pedicled nasoseptal flap was used for Grades 2b and 3 leakages. Unused septal bones and nasoseptal flaps were repositioned. Conclusion : Modified classification of intraoperative CSF leaks and tailored repair technique in a multilayered fashion using an en-bloc harvested septal bone and vascularized nasoseptal flaps is an effective and reliable method for the prevention of postoperative CSF leaks.

• Toxicological Research
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• v.16 no.4
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• pp.255-261
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• 2000

To investigate what kinds effect arsenic exert on the proliferation and differentiation of bone marrow cells to the neutrophilic granulocytes lineage cells, we treated sodium arsenite to murine bone marrow cells without or with the stimulation of G-CSF. When we added the various concentrations oj sodium arsenite to bone marrow cells without the stimulation of G-CSF for I, 3, 5 or 7 days, sodium arsenite did not make an any effect up to 2.5 $\mu\textrm{M}$$\mu\textrm{M}$$\mu\textrm{M}$$\mu\textrm{M}$$\mu\textrm{M}$$m\ell$ of G-CSF was induced by the co treatment of 12.5 $\mu\textrm{M}$

• BMB Reports
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• v.52 no.5
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• pp.336-341
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• 2019

The cGAS-STING pathway plays an important role in pathogen-induced activation of the innate immune response. The 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) found predominantly in the synovial fluid of osteoarthritis (OA) patients increases the expression of catabolic factors via the toll-like receptor-2 (TLR-2) signaling pathway. In this study, we investigated whether 29-kDa FN-f induces inflammatory responses via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway in human primary chondrocytes. The levels of cGAS and STING were elevated in OA cartilage compared with normal cartilage. Long-term treatment of chondrocytes with 29-kDa FN-f activated the cGAS/STING pathway together with the increased level of gamma-H2AX, a marker of DNA breaks. In addition, the expression of pro-inflammatory cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF-2), granulocyte colony-stimulating factor (G-CSF/CSF-3), and type I interferon ($IFN-{\alpha}$), was increased more than 100-fold in 29-kDa FN-f-treated chondrocytes. However, knockdown of cGAS and STING suppressed 29-kDa FN-f-induced expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ together with the decreased activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and inhibitor protein ${\kappa}B{\alpha}$ ($I{\kappa}B{\alpha}$). Furthermore, NOD2 or TLR-2 knockdown suppressed the expression of GM-CSF, G-CSF, and $IFN-{\alpha}$ as well as decreased the activation of the cGAS/STING pathway in 29-kDa FN-f-treated chondrocytes. These data demonstrate that the cGAS/STING/TBK1/IRF3 pathway plays a critical role in 29-kDa FN-f-induced expression of pro-inflammatory cytokines.

• 한국생물공학회:학술대회논문집
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• 2001.11a
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• pp.206-209
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• 2001

Recombinant human GM -CSF was expressed and secreted from transgenic rice cell suspension cultures in its biologically active form. This was accomplished by transforming rice callus tissues with an expression vector, pMYN44. containing the hGM -CSF cDNA. Regulated expression and secretion of hGM -CSF from this vector achieved using the promoter, signal peptide, and terminator from a rice alfa-amylase gene Amy3D. The Amy3D gene is expressed in response to sugar deprivation. The recombinant hGM -CSF was expressed from the transgenic rice cell culture on the sugar-free medium as a yield of about 110 mg/L in the culture filtrate, which was determined by ELISA. Biological activity of hGM-CSF was confirmed by measuring the proliferation of the hGM -CSF dependent TF -1 cells.(This work was supported by a grant from the NRL program of the Korean Ministry of Science and Technology. Shin, Y.- J.. Lee. J.-H and Kwon, T.-H. have been supported by BK21 program from the Korean Ministry of Education)