• Toxicological Research
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• 제23권4호
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• pp.383-389
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• 2007

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) regulates proliferation and differentiation of hematopoietic progenitor cells and modulates function of the mature hematopoietic cells. In the previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study we examined the single and repeated dose toxicity of rice cells-derived hGM-CSF in SD rats. During single dose toxicity study for 7 days, there were no any toxic effects at any dose of from 10 to $1000{\mu}g/kg$. The lethal dose ($LD_{50}$) was not found in this range. Moreover, repeated dose toxicity study of 14-days period and at the doses of 50 and $200{\mu}g/kg$ (i. v.) of rhGM-CSF did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the test groups. The hematological and blood biochemical parameters were statistically not different in all the groups. These results suggest that rhGM-CSF has no toxicity in SD rats.

• Toxicological Research
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• 제24권4호
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• pp.315-320
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• 2008

Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) is a glycoprotein and hematopoietic growth factors that regulates the proliferation of myeloid precursor cells and activates mature granulocytes and macrophages. In a previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study, we examined the repeated dose toxicity of rhGM-CSF in SD rats. The repeated dose toxicity study was performed at each dose of 50 and 200 ${\mu}g/kg$ subcutaneous administration of rhGM-CSF everyday for 28-days period. The results did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the tested groups. The hematological and blood biochemical parameters were statistically not different in all groups. These results suggest that rhGM-CSF may show no repeated dose toxicity in SD rats under the conditions.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1185-1189
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• 2015

Background: Chemotherapy-induced febrile neutropenia (FN) with solid tumors causes mortality and morbidity at a significant rate. The purpose of this study was to compare the effects of filgastrim and lenograstim started with the first dose of antibiotics in hospitalized patients diagnosed with FN. Materials and Methods: Between February 2009 and May 2012, 151 patients diagnosed with FN were evaluated, retrospectively. In those considered appropriate for hospitalization, convenient antibiotic therapy with granulocyte colony stimulating factors was started within first 30 minutes by completing necessary examinations in accordance with FEN guide recommendations. Results: In this study, 175 febrile neutropenia attacks in 151 patients were examined. Seventy three of the patients were male and 78 were female. The average age was 53.6 and 53.6, respectively. The most common solid tumor was breast carcinoma in 38 (25%). One hundred and five FN patients (58%) were those who received granulocyte colony stimulating factors as primary prophylaxis. Conclusions: While studies comparing both drugs generally involve treatments started for prophylaxis, this study compared the treatment given during the febrile neutropenia attack. Compared to lenograstim, filgastrim shortens the duration of hospitalization during febrile neutropenia attack by facilitating faster recovery with solid tumors.

• IMMUNE NETWORK
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• 제6권1호
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• pp.13-19
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• 2006

Background: Granulocyte colony stimulating factor (G-CSF) is known as a cytokine central to the hematopoiesis of blood cells and to modulate their cellular functions. Besides granulocytes and their precursors, monocytes/macrophages and endothelial cells are direct target cells of G-CSF action. G-CSF influences immune cells in an anti inflammatory way. Methods: To evaluate whether G-CSF has a potential for preventing or ameliorating diseases characterized by mucosal inflammation, we used a mouse model with trinitrobenzene sulfonic acid (TNBS)-induced inflammatory colitis. To the mice model G-CSF was administrated daily by intraperitoneal injection. Macroscopic evaluation and immunohistochemical analysis of colonic tissues were performed. Results: Re combinant human G-CSF significantly inhibited LPS-induced TNF-${\alpha}$ mRNA expression in THP-1 cells. As for in vivo relevance, G-CSF dramatically reduced the weight loss of mice, colonic damage, and mucosal ulceration that characterize TNBS colitis. Moreover, G-CSF suppressed the expression of tumor necrosis factor-${\alpha}$, interleukin-$1{\beta}$, and intercellular adhesion molecule-1 in TNBS colitis. Conclusion: Current results demonstrate that G-CSF may be an effective agent for the treatment of diseases characterized by mucosal inflammation.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2002년도 생물공학의 동향 (X)
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• pp.325-328
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• 2002

Sucrose 의 경우 저농도에서는 후반부로 갈수록 세포생장 속도는 현저히 감소하는데 비해 hGM-CSF 생산은 후반부에 급격히 증가함을 확인하였다. 고농도 sucrose를 사용하는 경우에는 lag phase가 길어지는 동안에 hGM-CSF의 생산이 증가하였다. 따라서 배양 초기에는 고농도 sucrose가, 배양 후반에는 저농도 sucrose로 존재하는 경우에 hGM-CSF를 많이 얻을 수 있었다. Nitrogen source의 농도는 60.52 mM과 121.04 mM일 때가 세포의 생장이나 hGM-CSF의 생산을 증가시켰으며, phosphate의 경우에는 4.96 mM 일 때가 대조구인 2.48 mM 일 때보다 hGM-CSF의 생산을 3 배 증가시켰다.

• Applied Microscopy
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• 제33권2호
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• pp.131-143
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• 2003

메뚜기 체내와 체외에서 혈구 분화경로를 광학현미경과 전자현미경으로 관찰하였다. 조혈기관에서 혈구의 형성은 망상세포에 둘러싸인 줄기세포에서부터 유래되었으며, 줄기세포에서부터 원시혈구, 무정형혈구, I형 과립혈구, II형 과립혈구, 소구혈구 및 편도혈구가 각각 분화되는 것을 확인하였다. 곤충배지에 배양된 조혈조직에서 각각 다른 형태의 혈구들이 분화되어 방출되었다. 그러나, 이들 혈구들의 유사분열상은 관찰되지 않았다. 배지의 조혈기관에서 분화된 세포들의 형태학적 특징들은 메뚜기 체내의 조혈기관에서 분화된 세포들과 같았다. 이와 같은 결과는 줄기세포가 각각의 서로 다른 혈구들로 직접 분화하는 것을 의미한다. 본 연구 결과 조혈기관의 줄기세포는 각각의 혈구로 직접 분화할 수 있는 기능을 가지고 있었으며, 체내와 체외에서 한번 형성된 순환 혈구는 다른 혈구의 형태로 변형되지 않았다. 메뚜기에서 순환혈구의 유지는 복부 등쪽 첫 번째 마디에서 여덟 번째 마디 사이의 익상근 위에 광범위하게 존재하고 있는 조혈기관에 전적으로 의존하였다.

• Journal of Ginseng Research
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• 제44권2호
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• pp.274-281
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• 2020

Background: Ultraviolet (UV) goes through the epidermis and promotes release of inflammatory cytokines in keratinocytes. Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of the keratinocyte-derived cytokines, regulates proliferation and differentiation of melanocytes. Extracellular signal-regulated kinase (ERK1/2) and protein kinase C (PKC) signaling pathways regulate expression of GM-CSF. Based on these results, we found that ginsenoside Rh3 prevented GM-CSF production and release in UV-B-exposed SP-1 keratinocytes and that this inhibitory effect resulted from the reduction of PKCδ and ERK phosphorylation. Methods: We investigated the mechanism by which ginsenoside Rh3 from Panax ginseng inhibited GM-CSF release from UV-B-irradiated keratinocytes. Results: Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or UV-B induced release of GM-CSF in the SP-1 keratinocytes. To elucidate whether the change in GM-CSF expression could be related to PKC signaling, the cells were pretreated with H7, an inhibitor of PKC, and irradiated with UV-B. GM-CSF was decreased by H7 in a dose-dependent manner. When we analyzed which ginsenosides repressed GM-CSF expression among 15 ginsenosides, ginsenoside Rh3 showed the largest decline to 40% of GM-CSF expression in enzyme-linked immunosorbent assay. Western blot analysis showed that TPA enhanced the phosphorylation of PKCδ and ERK in the keratinocytes. When we examined the effect of ginsenoside Rh3, we identified that ginsenoside Rh3 inhibited the TPA-induced phosphorylation levels of PKCδ and ERK. Conclusion: In summary, we found that ginsenoside Rh3 impeded UV-B-induced GM-CSF production through repression of PKCδ and ERK phosphorylation in SP-1 keratinocytes.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.377-384
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• 1998

Gold compounds depress phagocytic cell responses, including chemotaxis, and respiratory burst. However, the effects of gold compounds on the function of phagocytic cells are variable according to the preparation of medicine. In this study, effect of tetrachloroauric acid on activated neutrophil responses, including respiratory burst, lysosomal enzyme release and change of intracellular $Ca^{2+}$ level and on the synthesis of interleukin-8 and granulocyte-macrophage colony stimulating factor by macrophages was studied. This study further examines how gold compounds affect the activation processes. The respiratory burst stimulated by complement C5a, degraded IgG and PMA in neutrophils was inhibited by tetrachloroauric acid. In contrast to C5a and degraded IgG, PMA-stimulated superoxide production was weakly inhibited by tetrachloroauric acid. Staurosporine, genistein, EGTA and verapamil inhibited superoxide and $H_2O_2$ production caused by C5a and degraded IgG. PMA-stimulated superoxide production was inhibited by staurosporine but was not affected by genistein. Tetrachloroauric acid, genistein, EGTA and verapamil inhibited the release of acid phosphatase and myeloperoxidase, while the effect of staurosporine was not detected. The synthesis of interleukin-8 and granulocyte-macrophage colony stimulating factor by $interleukin-1{\beta}$ in macrophages was inhibited by tetrachloroauric acid. Preincubation with tetrachloroauric acid, genistein, EGTA and verapamil, the elevation of [$Ca^{2+}_i$] evoked by C5a was inhibited. Store-regulated $Ca^{2+}$ entry in thapsigargin-pretreated neutrophils was decreased by the addition of tetrachloroauric acid and genistein. The effect of staurosporine on intracellular $Ca^{2+}$ mobilization was not observed. In conclusion, tetrachloroauric acid may suppress neutrophil responses through its inhibitory action on elevation of intracellular $Ca^{2+}$ level and protein kinase C. It might exhibit an inhibitory effect on the action of protein tyrosine kinase. Tetrachloroauric acid depresses cytokine production by macrophages.

• Biomolecules & Therapeutics
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• 제10권4호
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• pp.268-273
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• 2002

Mutagenic potential of HM10411 (recombinant human granulocyte colony stimulating factor) was evaluated by bacterial reverse mutation test, in vitro chromosome aberration test and in vivo micronucleus test. The bacterial reverse mutation test was performed using the histidine auxotroph strains of Salmonella typhimurium TA100, TA1535, TA98, TA1537 and tryptophan auxotroph strain of Escherichia coli WP2 uvrA. The negative results of the bacterial reverse mutation test suggest that HM10411 does not induce mutation, in the genome of Salmonella typhimurium and E. coli under the conditions used. In addition, it has little clastogenicity either in vitro chromosome aberration test or in vivo micronucleus test. For in vitro chromosomal aberration test, Chinese hamster lung(CHL) cells were exposed to HM10411 of 23, 46 or 92 $\mu\textrm{g}$/ml for 6 or 24 hours in the absence and for 6 hours in the presence of metabolic activation system. There was no significant increase in the number of aberrant metaphase in HM 10411-treated groups at any dose levels both in the presence and absence of metabolic activation system. The micronucleus test was carried out using specific pathogen free(SPF) 7-week old male ICR mice, The test item, HM10411 was intraperitoneally administered at 1150, 2300 or 4600 $\mu\textrm{g}$/kg once a day for 2 consecutive days. There was no significant increase in the frequencies of micronucleated polychromatic erythrocytes(PCEs) at any treated groups compared with negative control group. Therefore, these results demonstrate that the test item, HM10411, was not mutagenic under the condition of these studies.

• Journal of Nutrition and Health
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• 제38권8호
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• pp.649-655
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• 2005

Nutrigenomics refers to research that investigates the interaction between nutrition and the human genome. Caffeine in tea and coffee is widely and routinely consumed by people. This study was performed to confirm the effect of caffeine treatment on the gene expression and cytokine profiling in 3T3-L1 adipocyte cells using microarray and protein array methodology. Treatment of caffeine in 3T3-L1 adipocyte cells increased expression of several genes related with obesity including adipocyte C1Q and collagen domain containing (ACDC), Adipsin (ADN), uncoupling protein 3(UCP3), while glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which is known as lipid storage enzyme, was decreased by caffeine treatment. Furthermore, cytokines, such as interleukin-3 (IL-3), interleukin-12(IL-12), interleukin-13 (IL-13), granulocyte colony stimulating factor (GCSF), granulocyte macrophage colony stimulating factor (GM-CSF) and vascular endothelial growth factor (VEGF), were decreased in caffeine treated 3T3-L1 adipocyte cells. These results provided interesting information about the genes related with caffeine and cytokine expression profiling in obesity.