• BMB Reports
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• v.50 no.4
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• pp.208-213
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• 2017

Vascular endothelial growth factor (VEGF) is an essential cytokine that has functions in the formation of new blood vessels and regression of cardiac hypertrophy. VEGF/VEGF-receptor-1 (VEGFR1) signaling plays a key role in the regression of cardiac hypertrophy, whereas VEGF/VEGFR2 signaling leads to cardiac hypertrophy. In this study, we identified the prohypertrophic role of miR-374 using neonatal rat ventricular myocytes (NRVMs). Our results showed that overexpression of miR-374 activated G protein-coupled receptor-mediated prohypertrophic pathways by the inhibition of VEGFR1-dependent regression pathways. Luciferase assays revealed that miR-374 could directly target the 3'-untranslated regions of VEGFR1 and cGMP-dependent protein kinase-1. Collectively, these findings demonstrated that miR-374 was a novel pro-hypertrophic microRNA functioning to suppress the VEGFR1-mediated regression pathway.

• Nutrition Research and Practice
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• v.12 no.1
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• pp.20-28
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• 2018

BACKGROUND/OBJECTIVES: Perilla frutescens (L.) Britton var. (PF) sprout is a plant of the labiate family. We have previously reported the protective effects of PF sprout extract on cytokine-induced ${\beta}-cell$ damage. However, the mechanism of action of the PF sprout extract in type 2 diabetes (T2DM) has not been investigated. The present study was designed to study the effects of PF sprout extract and signaling mechanisms in the T2DM mice model using C57BL/KsJ-db/db (db/db) mice. MATERIALS/METHODS: Male db/db mice were orally administered PF sprout extract (100, 300, and 1,000 mg/kg of body weight) or rosiglitazone (RGZ, positive drug, 1 mg/kg of body weight) for 4 weeks. Signaling mechanisms were analyzed using liver tissues and HepG2 cells. RESULTS: The PF sprout extract (300 and 1,000 mg/kg) significantly reduced the fasting blood glucose, serum insulin, triglyceride and total cholesterol levels in db/db mice. PF sprout extract also significantly improved glucose intolerance and insulin sensitivity, decreased hepatic gluconeogenic protein expression, and ameliorated histological alterations of the pancreas and liver. Levels of phosphorylated AMP-activated protein kinase (AMPK) protein expression also increased in the liver after treatment with the extract. In addition, an increase in the phosphorylation of AMPK and decrease in the phosphoenolpyruvate carboxykinase and glucose 6-phosphatase proteins in HepG2 cells were also observed. CONCLUSIONS: Our results sugges that PF sprout displays beneficial effects in the prevention and treatment of type 2 diabetes via modulation of the AMPK pathway and inhibition of gluconeogenesis in the liver.

• IMMUNE NETWORK
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• v.6 no.1
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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.

• Nutritional Sciences
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• v.5 no.2
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• pp.60-67
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• 2002

Paeonia japonica var. pilosa $N_{AKAI}$, (PJ; Baek-Jak-Yak) is a medicinal plant which has been widely used as a component or blood-building decoctions. This study was performed to investigate the immunomodulative effects of PJ in mice, using in vitro and in vivo experiments. The immunomodulative effects were studied in vitro by determining the proliferation or mice splenocytes and the production of three kinds of cytokines (IL-1$\beta$, IL-6, TNF-$\alpha$) by mire peritoneal macrophages which were cultured with sequential fractions of PJ methanol extract (methanol, hexane, chloroform, ethylacetate, butanol and water). In an in vivo experiment using mice, different concentrations of PJ water extract were orally administrated every other day for two weeks. The production of cytokines (IL-1$\beta$, IL-6, TNF-$\alpha$) secreted by activated macrophages, and the proliferation of mice splenocytes, were used as indices for immunocompetence. In vitro supplementation using a hexane fraction of PJ in the range of 1 to 100 $\mu$ g/ml enhanced splenocyte proliferation by 1.8 to 12%, and by 10-15% using an aqueous fraction, compared to the control. IL-l$\beta$ production was significantly increased with the supplementation of butanol, hexane and water extracts of PJ Higher levels of IL-6 production were detected with supplementation of chloroform or water extracts. However, there were no significant differences in the production of TNF-$\alpha$ among the treated groups and the control. From the in vivo study, the highest proliferation of splenocytes was seen in the mice orally administrated with the PJ water extract at the concentration of 500 mg/kg body weight. In the case of cytosine production, IL-1-$\beta$, IL-6, and TNF-$\alpha$ released by activated peritoneal macrophages were augmented by the oral administration of a PJ water extract. These results indicate that Pl may enhance the immune function by regulating splenocyte proliferation and cytokine production capacity in mice.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.93-100
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• 2004

This study was carried out for analyzing pathological and epidemiological factors of osteoporosis and doing pilot test using trial compounds of tuna bone and oriental herbs based on the factors. Osteoporosis is originated from osteoblast, osteoclast, organic and inorganic factors etc. Therefore the pathology of osteoporosis is not simple because the cytokine, growth factors and hormones of the components are various a lot. Taking a view of epidemiological factors of type I osteoporosis, ageㆍmenarcheㆍcholesterolㆍBMI etc. have definite relation to them. So we can approach to aging or consumptive disease in oriental medicine, specifically differential diagnosis of blood depletion with deficiency of qi, deficiency of kidney, deficiency of yin, bony weakness etc. And it should be considered together with rules for maintaining good health or habit concomitantly. Therefore IL1ㆍ6 or TNF αㆍβ are generally used as molecular biological index for osteoblast and osteoclast because the most important index is bone mineral density and strength, but the factors like collagen and noncollagen protein must be accounted as biomarkers. Trial compounds generally showed favorable effects on accompanying subjective symptoms of osteoporosis in the pilot test for menopausal woman. But if she didn't have specific symptoms of osteoporosis there wasn't any specific change. And osteocalcin was increased in case of being under standard level, but wasn't changed in case of normal level. Therefore these trial compounds can be used as a funcdonal diet for type I osteoporotic patients or preventive measures.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.122-136
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• 2004

To evaluate effect of CRSST on inhibiting the occurrence of arthritis, we performed the experiments including production of inflammatory cytokine and immunoglobin in collagen induced arthritis model. The results were obtained as follows. CRSST extract shows any cytotoxicity effect on mouse lung fibroblast cells at dose of 400 ㎍/㎖. CRSST group shows inhibitory effect on arthritis incidence than control group for six weeks. Arthritis index of CRSST group reduces from 4 weeks (75±17.4%) to 6 weeks (33.3±10.0%) compared with control group. In CRSST group, production of cytokines which shows suppressive effect on inflammation (IL-4, IL-10 ) are increased and which promotes inflammation (TNF-α, INF-γ) are decreased in blood. In CRSST group, production of immunogloblin (IgG2b, IgG3 and IgM) is reduced compared with control group, and rate of CD4+ and CD3+ T cell is lower in joint and higher in lymph node compared with control group. From above results it could be accepted that CRSST shows anti-arthritis effect via immune system especially through the controlling the inflammatory cytokines and immunoglobins. CRSST could be usefully applied for the prevention and treatment of RA. And also is expected to be clinically helpful on the treatment of RA through modification.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.2
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• pp.340-345
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• 2008

Extract of Acanthopanax senticosus has recently been demonstrated to possess significant antidiabetic potential, in accordance with the traditional use of this plant as an antidiabetic natural health product. The present study evaluated the effects of fermented extract (FE) of this plant on glucose-stimulated insulin secretion, glucose uptake, and streptozotocin-induced type 1 diabetes model. A 3 h pretreatment with FE prevented $IL-1{\beta}$ and $IFN-{\gamma}$ toxicity in isolated rat islets. However, it did not affect insulin-stimulated glucose uptake in C2C12 myotubes. In addition, pretreatment of mice with FE blocked the destruction of streptozotocin-induced islets and the development of type 1 diabetes. FE reduced blood glucose level, increased insulin secretion, and improved glucose tolerance in streptozotocin-treated mice, whereas nonfermented extract (NFE) had moderate effects. Immunohistochemical staining for insulin clearly showed that pretreatment with FE blocked the STZ-induced islets destruction and restored the number of islet cells that secreted insulin to the level of the control. Although the active principles and their mechanisms of action remain to be identified, FE may nevertheless represent a novel complementary therapy and a source of novel therapeutic agents against type 1 diabetes mellitus.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.113-113
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• 1995

본 연구는 표고버섯에서 분리정제한 렉틴 성분(LEL)을 말초혈액 단핵세포(PBMC)에 반응시켜 사이토카인 유도능을 지질다당류(LPS)와 비교하여 역전사효소 중합반응법(RT-PCR)으로 측정하였다. 측정 대상 사이토카인은 IL-1, IL-2, IL-6, TNF$\alpha$ 및 IFN${\gamma}$의 다섯가지였으며 이들을 대상으로 PBMC에 렉틴을 적용하여 1, 8, 24, 48, 72, 96, 120분 등의 시간대에서 반응시켜 사이토카인의 유전자 발현 유도에 관한 다음의 결과를 얻었다. LEL의 사용 농도에 따른 편도선 림프구(tonsillar lymphocyte)의 TNF$\alpha$ 유전자 발현 양상은 반응 1시간의 경우 LEL의 일부 농도와 LPS 전농도에서 관찰되었으나 반응 40시간째에는 LEL 전농도와 LPS 전농도에서 TNF$\alpha$ 유전자 발현 양상을 관찰할 수 없었다. RT-PCR 결과 원액이나 회석액 재료로부터 관찰된 TNF$\alpha$유전자 band의 강 약 차이는 나타나지 않았다. LEL의 자극에 의한 반응 시간대 별 PBMC에 의한 사이토카인 유전자 발현 양상은 위에서 언급된 다섯가지 사이토카인을 유도, 생성할 수 있다는 것이 확인되었는데, IL-2, IL-6 및 IFN${\gamma}$는 120시간까지 장시간 지속되는 유전자 발현이 가능한 반면 TNF $\alpha$의 생성 양상은 이들 사이토카인의 생성 양상과는 판이하게 반응 1, 8 및 24 시간대까지만 TNF$\alpha$ 유전자 발현을 관찰할 수 있었고 IL-1은 72 시간까지 반응을 나타내는 등 특이적 양상을 보였다. 한편 LPS는 실험에 사용된 전 사이토카인의 유전자 발현을 120시간대까지 반응이 유지됨을 관찰하였기에 LPS가 PBMC의 강력한 사이토카인 유도체임을 입증할 수 있었으며 LEL과 다소 상이한 결과를 보였으나 LEL 또한 PBMC로부터 사이토카인을 생성 유지시킬 수 있는 유도체로 작용함을 확인할 수 있었다.

• Reproductive and Developmental Biology
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• v.34 no.4
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• pp.289-297
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• 2010

Erythropoietin (EPO) is a glycoprotein hormone secreted from primarily cells of the peritubular capillary endothelium of the kidney, and is responsible for the regulation of red blood cell production. We constructed and expressed dimeric cDNAs in Chinease hamster ovary (CHO) cells encoding a fusion protein consisting of 2 complete human EPO domains linked by a 2-amino acid linker (Ile-Asp). We described the activity of dimeric hyperglycosylated EPO (dHGEPO) mutants containing additional oligosaccharide chains and characterized the function of glycosylation. No dimeric proteins with mutation at the $105^{th}$ amino acid were found in the cell medium. Growth and differentiation of the human EPO-dependent leukemiae cell line (F36E) were used to measure cytokine dependency and in vitro bioactivity of dHGEPO proteins. MIT assay at 24 h increased due to the survival of F36E cells. The dHGEPO protein migrated as a broad band with an average molecular mass of 75 kDa. The mutant, dHGEPO, was slightly higher than the wild-type (WT) dimeri-EPO band. Enzymatic N-deglycosylation resulted in the formation of a narrow band with a molecular mass twice of that of of monomeric EPO digested with an N-glycosylation enzyme. Hematocrit values were remarkably increased in all treatment groups. Pharmacokinetic analysis was also affected when 2.5 IU of dHGEPO were intravenously injected into the tails of the mice. The biological activity and half-life of dHGEPO mutants were enhanced as compared to the corresponding items associated the WT dimeric EPO. These results suggest that recombinant dHGEPO may be attractive biological and therapeutic targets.

• Reproductive and Developmental Biology
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• v.30 no.1
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• pp.27-34
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• 2006

This study was conducted to compare the reproduction ability of the wild type boar and recombinant human erythropoietin (hEPO) transgenic boar semen. Ejaculated boar semen was analyzed by flow cytometry, Elisa and IVF methods. In experiment 1, flow cytometric analysis showed that the live sperm ratio of transgenic boar sperm significantly lower (P<0.05) than that of wild type boar after incubation at 20, 22, 24 and 26 hr. In experiment 2, the presence and levels of various cytokines (IL-6, IL-10 and $TNF-{\alpha}$) to related animal reproduction in the seminal and blood plasma were examined using specific enzyme immunoassay. There was no significant difference between both groups. In experiment 3, the fertilizing capacity and developmental ability of both boar sperm were compared. The transgenic boar sperm had a significantly low capacity of penetration, sperm-zona binding, embryo development, and blastocyst formation compared to wild type sperm (P<0.05). These results suggest that transgenic boar sperm harboring hEPO gene has low sperm viability than wild type boar, and it is a reason to decrease of fertility and litter size.