• 대한본초학회지
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• 제28권5호
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• pp.113-119
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• 2013

Objectives : The purpose of this study was to investigate the effects of Angelicae Gigantis Radix Water Extract(AG) on the production of proinflammatory mediators in RAW 264.7 cells stimulated with lipopolysaccharide(LPS). Method : RAW 264.7 cells were cotreated with AG(50 and 100 ug/mL) and lipopolysaccharide(LPS; 1 ug/mL) for 24 hours. After 24 hour treatment, using Bead-based multiplex cytokine assay, concentrations of various cytokines such as interleukin(IL)-6, IL-$1{\beta}$, IL-10, tumor necrosis factor-alpha(TNF-${\alpha}$), granulocyte colony-stimulating factor(G-CSF), granulocyte macrophage colony-stimulating factor(GM-CSF), interferon inducible protein-10(IP-10), leukemia inhibitory factor(LIF), lipopolysaccharide-induced chemokine(LIX), monocyte chemoattractant protein-1(MCP-1), macrophage colony-stimulating factor(M-CSF), macrophage inflammatory protein(MIP)-$1{\alpha}$, MIP-$1{\beta}$, MIP-2, Regulated on Activation, Normal T cell Expressed and Secreted(RANTES) and vascular endothelial growth factor(VEGF) were measured. Result : AG significantly inhibited LPS-induced production of TNF-${\alpha}$, MIP-$1{\alpha}$, G-CSF, RANTES, IL-10, and M-CSF from LPS-stimulated RAW 264.7 cells at the concentrations of 50 and 100 ug/mL. AG significantly inhibited LPS-induced production of MIP-$1{\beta}$, MIP-2, GM-CSF, and IL-6 from LPS-stimulated RAW 264.7 cells at the concentrations of 50 ug/mL. AG significantly inhibited LPS-induced production of VEGF from LPS-stimulated RAW 264.7 cells at the concentrations of 100 ug/mL. But AG did not show any significant effect on the production of MCP-1, LIF, LIX, IP-10 and IL-$1{\beta}$ from LPS-induced RAW 264.7 cells. Conclusion : These results suggest that AG has anti-inflammatory effect related with its inhibition of proinflammatory mediators such as TNF-${\alpha}$, MIP-$1{\alpha}$, G-CSF, RANTES, IL-10, MIP-$1{\beta}$, MIP-2, GM-CSF, IL-6, VEGF and M-CSF in LPS-induced macrophages.

• 약학회지
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• 제45권6호
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• pp.715-723
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• 2001

Indomethacin is well known as a prostaglandin (PG) E$_2$ synthetase inhibitor which has antipyretic and anti-inflammatory effects and reduces the risk of cancer Growing tumors greatly induce hypersensitive responses to lipopolysaccharide (LPS). Thus, this study was investigated the effect of indomethacin on the LPS-induced production of cytokines in sarcoma-bearing ICR mice. Indomethacin at doses of 5mg/kg was administered orally 30 minutes before i.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS remarkedly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$, levels in both serum and splenic supernatants compared with those in controls, while indomethacin significantly reduced the LPS-increased levels of IL-1$\beta$, in both serum and supernatants. LPS significantly enhanced IL-2 levels in serum and interferon (IFN)-${\gamma}$ levels in supernatants, whereas indomethacin did not affect the LPS-increased levels of IL-2 and IFN-${\gamma}$. These data, therefore, indicate that indomethacin may attenuate the pathogenesis of IL-1$\beta$, induced by LPS and maintain the tumoricidal cellular immune effects by LPS-increased production of IL- 2 and IFN-${\gamma}$ in tumor-bearing state.

• 동의신경정신과학회지
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• 제18권1호
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• pp.185-196
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• 2007

Objective : This experimental Study was designed to investigate the effects of FOENICULI FRUCTUS(FF) on the change of inhibition lactate dehydrogenase(LDH) activity in neuronal cells and cytokines production in serum of cerebral ischemic rats. Method : FOENICULI FRUCTUS(FF)freeze dry powder and FF on the LDH activity in neuronal cells. Changes of FF on the physiological parameters(PaO2, PaCO2, MABP and HR) in crerbral ischemic rats. Effects of FF on the IL-1beta production, $TNF-{\alpha}$ production, $TGF-{\beta}$ production, and IL-10 in serum of cerebral ischemic rats. MCAO :. cytokines production of serum by drawing from femoral arterial blood after MCAO 1 hr. Reperfusion : cytokines production of serum by drawing from femoral arterial blood after reperfusion 1 hr. Results and Conclusion : 1. FF did not inhibit lactate dehydrogenase(LDH) activity in neuronal cells. 2. In serum by drawing from femoral arterial blood after middle cerebral arterial occlusion(MCAO) 1 hr and reperfusion 1 hr, sample group was significantly decreased $IL-l{\beta}$ production compared with control group 3. In serum by drawing from femoral arterial blood after MCAO 1 hr and reperfusion 1 hr, sample group was significantly decreased $TNF-{\alpha}$ production compared with control group. 4. In serum by drawing from femoral arterial blood after MCAO 1 hr and reperfusion 1 hr, sample group was significantly increased $TGF-{\beta}$ production compared with control group. 5. In serum by drawing from femoral arterial blood after reperfusion 1 hr, sample group was significantly increased IL-10 production compared with control group. This results were suggested that FF had inhibitive effect on the brain damage by inhibited LDH activity, $IL-l{\beta}$ and $TNF-{\alpha}$production, but accelerated $TGF-{\beta}$ production and IL-10 production.

• 동의생리병리학회지
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• 제19권5호
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• pp.1225-1232
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• 2005

Based on traditional medicine theories, GC, an extract from 5 herbs, has been formulated and prescribed for the treatment of human rheumatoid arthritis(hRA) for many years. The present studies was done to investigate whether GC has inhibitory effects on activation of fibroblast-like sinoviocytes isolated from a RA patient. In tumor necrosis factor-${\alpha}(TNF-{\alpha}$)/ interleukin-IL-$1{\beta}$(IL-$1{\beta}$) treated human sinoviocytes, the mRNA expression of molecular indicators related to pathologic changes of the sinoviocytes were examined using quantitative real-time PCR. The treatment of GC($10{\mu}g/ml$) significantly suppressed the expression of proinflammatory cytokines and chemokines such as $TNF-{\alpha}$, IL-6 and IL-8 compared with the control, but not $IL-1{\beta}$, The mRNA level of intracellular adhesion molecule-1 (ICAM-1) which is known to increase in the activated sinoviocytes of RA patients, was slightly decreased by GC. The expression of NOS-II was considerably reduced, which was accompanied by a decrease in the production of nitric oxide(NO). Furthermore, GC dramatically raised the mRNA levels of tissue inhibitors of matrix metalloproteinase-1 (TIMP-1), while those of matrix metalloproteinase-3 were significantly lowered. Taken together, these data suggested that GC might suppress the activation of sinoviocytes in hRA.

• 사상체질의학회지
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• 제12권1호
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• pp.186-200
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• 2000

소양인(少陽人) 인동등지골피탕(忍冬藤地骨皮湯)이 중소(中消) 합병증(合倂症)에 미치는 영향(影響)을 살펴보고자 하였고 결과(結果)는 다음과 같다. 1. 장관운동(腸管運動)을 억제(抑制)하였다. 2. Acetic acid에 의한 writhing syndrome을 억제(抑制)하였다. 3. Evans blue에 의한 모세혈관투과성(毛細血管透過性)을 억제(抑制)하였다. 4. Histamine에 의한 급성족부종(急性足浮腫)을 억제(抑制)하였다. 5. Cotton pellet에 의한 육아종(肉芽腫) 형성(形成)을 억제(抑制)하였다. 6. 흉선세포(胸線細胞) 및 비장세포(脾臟細胞)의 세포생존율(細胞生存率)을 증가(增加)시켰다. 7. 흉선세포(胸線細胞)로부터 ${\gamma}-IFN$ 및 IL-2의 분비(分泌)를 억제(抑制)하였다. 8. 비장세포(脾臟細胞)로부터 IL-4의 분비(分泌)는 증가(增加)시켰으나, $TNF-{\alpha}$ 및 $IL-1{\beta}$의 분비(分泌)는 억제(抑制)하였다. 9. 복강(腹腔) 대식세포(大食細胞)로부터 $TNF-{\alpha}$, $IL-1{\beta}$ 및 nitric oxide의 분비(分泌)를 억제(抑制)하였다. 10. 복강(腹腔) 대식세포(大食細胞)의 lucigenin chemiluminescence 및 FITC-conjugated E. cole engulfment를 촉진(促進)하였다. 이상의 실험(實驗) 결과(結果) IJTE는 장관운동(腸管運動)을 억제(抑制)하였으며, 진통(鎭痛) 및 항염작용(抗炎作用)을 나타냈고, 이들 작용은 면역세포(免疫細胞)로부터 $TNF-{\alpha}$, $IL-1{\beta}$ 및 nitric oxide의 생성(生成)을 억제(抑制)하기 때문인 것으로 추정된다. 따라서 이러한 기전(機轉)에 의하여 인동등지골피탕(忍冬藤地骨皮湯)은 중소(中消) 합병증(合倂症)의 하나인 염증(炎症)을 억제(抑制)하는데 유효(有效)한 것으로 사료(思料)된다.

• Pediatric Infection and Vaccine
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• 제12권1호
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• pp.75-85
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• 2005

목 적 : 혈액종양 환아의 항암요법 후 발생한 호중구감소증 상태에서, 진균 감염은 높은 치명률을 가지는 것으로 알려져 있다. 진균 감염에 대한 경험적 항진균제로 주로 사용되는 ABV는 염증성 사이토카인인 IL-$1{\beta}$, TNF-${\alpha}$의 증가에 의해 발생하는 것으로 알려져 있는 발열, 오한, 발진, 신독성과 같은 부작용이 있다. Azole 계열의 ITZA도 광범위한 항진균 효과를 나타내고 있어 경험적 항진균제로의 사용이 고려되고 있는데 본 연구는 ABV와 ITZA의 정맥 주입에 따른 부작용의 발생 및 효능과 염증성 사이토카인 및 항염증성 사이토카인의 변화를 관찰하고자 한다. 방 법: 2004년 3월부터 2005년 2월까지 호중구감소증 상태에서 발열이 있어 치료한 급성 백혈병 환자를 대상으로 하였다. 대상으로 선정된 환자는 30명으로 ABV, ITZA 각각의 치료군은 15명이었다. 항진균제는 총 14일간 투여하였으며, 투여 후 혈청에 포함된 염증성 사이토카인(IL-$1{\beta}$, TNF-${\alpha}$)과 항염증성 사이토카인(IL-1Ra, IL-4)을 ELIZA를 통하여 측정하고, 치료 종료 시 치료 효과를 평가하였다. 결 과 : 두 치료군의 성별, 나이, 진단명, 항암치료의 단계, 마지막 항암요법의 시기 특성은 유의한 차이가 없었다. ABV 치료군에 비해 ITZA 치료군에서 정맥 주입 시 발생하는 이상 반응의 빈도가 적었다. 또한, ABV 치료군에서 ITZA 치료군에 비해 염증성 사이토카인인 IL-$1{\beta}$가 정맥주입 시 증가함을 보였고, IL-1Ra/IL-$1{\beta}$는 ABV 치료군에서는 감소하는 반면 ITZA 치료군에서는 증가함을 보였다. 결 론: 급성백혈병 소아에서 발열을 동반한 호중구감소증시 경험적 항진균제로 ABV와 ITZA를 사용하여 최종 치료 효과의 유의한 차이는 없었으나 정맥 투여와 연관된 이상 반응은 ABV 군에서 많았으며 호중구의 회복은 ITZA 군에서 빠른 것을 알 수 있었다. 이는 ABV나 ITZA 투여 시 시간에 따른 IL-Ra/IL-$1{\beta}$의 변화와 연관이 있을 것으로 생각된다.

• 약학회지
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• 제52권1호
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• pp.73-78
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• 2008

Immune system can protect host attacking from a variety of microorganism and virus through innate and adaptive immunities. The innate immune system can be activated by recognition of conserved carbohydrates on the cell surface of pathogen resulting in protection, immunity regulation and inflammation. Immunostimulating and anti-tumor ${\beta}$-glucan, major cell wall component of many fungi, could be recognized as pathogen associated molecular pattern (PAMP) by C-type lectin such as pathogen recognition receptor (PRR) of host innate immunity cells. In spite of many studies of basidiomycetes ${\beta}$-glucan on immunostimulation, little is known about the precise mechanism as molecular-level. Among C-type lectins, dectin-1 was cloned and reported as a ${\beta}$-glucan receptor. In this report, we demonstrated induction of cytokine gene transcription by Ganoderma lucidum ${\beta}$-glucan in the absence or presence of lipopolysaccharide (LPS) by RT-PCR analysis. The expression of murine dectin-1 (MD-1) on RAW264.7 macrophage by RT-PCR showing both the full length, 757 bp $(MD-1{\alpha})$ and alternative spliced form, 620 bp $(MD-1{\beta})$. Both $MD-1{\alpha}$ and $MD-1{\beta}$ mRNAs were induced by ${\beta $-glucan both in the absence and presence of LPS. To explore expression of inflammatory cytokines by ${\beta}$-glucan, RAW264.7 cells were treated with ${\beta}$-glucan for 12 hours. As a result, the expressions of IL-1 IL-6, IL-l0 and $TNF-{\alpha}$ were increased by ${\beta}$-glucan treatment in a dose-dependent fashion. From these results, ${\beta}$-glucan induced transcriptions of dectin-1 and immune activating cytokine genes, indicating induction of immune allertness by expressing dectin-1 and secreting inflammatory cytokines.

• Journal of Ginseng Research
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• 제41권4호
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• pp.513-523
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• 2017

Background: Korean Red Ginseng extracts (RGE) have been suggested as effective immune modulators, and we reported that ginsenosides possess anti-inflammasome properties. However, the properties of nonsaponin components of RGE have not been well studied. Methods: To assess the roles of nonsaponin fractions (NS) in NLRP3 inflammasome activation, we treated murine macrophages with or without first or second inflammasome activation signals with RGE, NS, or saponin fractions (SF). The first signal was nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$)-mediated transcription of pro-interleukin (IL)-$1{\beta}$ and NLRP3 while the second signal triggered assembly of inflammasome components, leading to IL-$1{\beta}$ maturation. In addition, we examined the role of NS in IL-6 production and IL-$1{\beta}$ maturation in mice. Results: NS induced IL-$1{\beta}$ and NLRP3 transcription via toll-like receptor 4 signaling, whereas SF blocked expression. During the second signal, SF attenuated NLRP3 inflammasome activation while NS did not. Further, NS-injected mice presented increased IL-$1{\beta}$ maturation and IL-6 production. Conclusion: SF and NS of RGE play differential roles in the NLRP3 inflammasome activation. Hence, RGE can be suggested as an NLRP3 inflammasome modulator.

• 동의신경정신과학회지
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• 제23권1호
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• pp.145-159
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• 2012

Objectives : This research investigates the effect of the JCT extract regarding Alzheimer's disease. Methods : The effects of the JCT extract on IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, NOS-II mRNA, APP mRNA, BACE mRNA, Nitric oxide(NO), and ${\beta}A$ protein production in the BV2 microglia cell lines treated with LPS and ${\beta}A$ were investigated. Results : 1. The JCT extract suppressed the expression of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, and NOS-II mRNA in BV2 microglial cell line treated with LPS and ${\beta}A$. 2. The JCT extract suppressed the expression of BACE and APP mRNA in BV2 microglial cell line treated with LPS and ${\beta}A$. 3. The JCT extract suppressed the expression of Nitric oxide(NO) in BV2 microglial cell line treated with LPS and ${\beta}A$. 4. The JCT extract suppressed the expression of ${\beta}A$ protein production in BV2 microglial cell line treated with LPS and ${\beta}A$. Conclusions : These results suggest that the JCT group may be effective for the treatment of Alzheimer's disease. Thus, JCT could be considered among the future therapeutic drugs indicated for the treatment of Alzheimer's disease.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.52-52
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• 2003

Granulocyte-macrophage colony stimulating factor (GM-CSF) is synthesized in the female reproductive tract and has been shown to play an important role in human and murine embryo development and implantation. However, the mechanism of GM-CSF on the embryo development is unknown. Recent studies suggested that GM-CSF may be increase the expression of implantation relented genes, such as interleukin-1 (IL-1) system. Our aim of this study was to compare the interleukin-1$\alpha$ (IL-1$\alpha$), interleukin-1$\beta$ (IL-1$\beta$) and interleukin-1 receptor antagonist (IL-lra) mRNA between the GM-CSF supplemented group and control group in mouse embryos. Mouse 2-cell embryos were cultured in P-1 medium supplemented with or without mouse GM-CSF (10 ng/ml). The number of total and apoptotic cell in blastocyst were assessed by TUNEL. And then, the expression of IL-1$\alpha$, IL-1$\beta$ and IL-1ra mRNA in blastocyst were examined by RT-PCR.