• IMMUNE NETWORK
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• 제7권1호
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• pp.31-38
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• 2007

Background: Mizoribine (MZR) is an imidazole nucleoside isolated from Eupenicillium brefeldianum. MZR is currendy in clinical use for patients who have undergone renal transplantation. Therapeutic efficacy of MZR has also been demonstrated in rheumatoid arthritis and lupus nephritis. MZR has been shown to inhibit the proliferation or lymphocytes by interfering with inosine monophosphate dehydrogenase. Since the exact mechanism by which MZR benefits rheumatoid arthritis (RA) is not clear, we investigated the ability of MZR to direct its immunosuppressive influences on other antigen presenting cells, such as macrophages. Methods: Mouse macrophage RAW264.7 cells were stimulated with lipopolysaccharide in the presence of MZR. To elucidate the mechanism of the therapeutic efficacy in chronic inflammatory diseases, we examined the effects of MZR on the production of pro-inflammatory cytokines, nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in macrophages. Results: MZR dose-dependendy decreased the production of nitric oxide and pro- inflammatory cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukins $1{\beta}$ (IL-${\beta}$ and IL-6 $PGE_2$. Examination of gene expression levels showed that the anti-inflammatory effect correlated with the down-regulation of inducible nitiric oxide synthase expression, cycloxygenase-2 expression and TNF-${\alpha}$ gene expression. Conclusion: In this work, we resulted whether MZR $(1.25{\sim}10{\mu}g/ml)$ inhibited macrophage activation by inhibiting secretion of pro-inflammatory cytokines, NO and $PGE_2$. These findings provide an explanation for the therapeutic efficacy of MZR in chronic inflammation-associated diseases.

• 한국식품위생안전성학회지
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• 제15권1호
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• pp.30-35
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• 2000

본 연구는 대장균 내독소로 실험적 패혈증을 유도한 토끼를 이용하여 지질성분과 cytokines에 대한 박테리아 내독소의 영향과 이 물질들 변화간의 상호 관련성을 조사한 결과이다. 내독소 투여군의 중성지방 및 콜레스테롤 농도는 전 검체채취 시간대에서 대조군보다 대체적으로 높았다(p<0.01 또는 0.05). 내독소 투여군의 인지질 농도는 내독소 투여후 3 및 6 시간대에 용량의존성으로 대조군보다 높았다(p<0.05). Tumor necrosis factor-$\alpha$ TNF-$\alpha$)와 interleukin-I$\beta$(IL-l$\beta$) 농도는 모든 검체채취 시기에서 대조군보다 증가하였다(p＜0.01 또는 0.05). 지질성분들의 변화와 cytokines(TNF-$\alpha$ 나 IL-1$\beta$)변화간에 유의한 음의 상관성이 있었으며(p<0.05), 중성지방이나 콜레스테롤 농도가 보다 높았던 내독소 투여 토끼들이 그렇지 않은 토끼들보다 상대적으로 더 좋은 임상상태를 보였다. 본 연구결과는 내독소에 의한 지질성분들의 변화가 지질 대사계의 혼란이라기보다 숙주 방어기작의 능동적 작용일 수도 있음을 시사하고 있다.

• Journal of Nutrition and Health
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• 제37권1호
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• pp.23-30
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• 2004

Ginger (Zingiber officinale Roscoe) has been used as a raw material in many traditional preparations since the ancient time. As a component of traditional health products, Ginger is known to be effective as appetite enhancer, anticold and anti-inflammation. This study was performed to investigate the immunomodulative effects of Ginger in mouse, using in vitro and ex vivo experiments. In vitro experiment, the mice splenocytes proliferation and three kinds of cytokines (IL-1 $\beta$, IL-6, and TNF-$\alpha$) prodution by peritoneal macrophages cultured with ethanol and water extracts of Ginger were used to indicate the immunomodulative effect. In order to elucidate the immunomodulative effects of Ginger ex vivo, water extract of Ginger was orally administrated into mice, and isolated splencytes and macrophages were used as experimental model. Ex vivo experiment, six to seven week old mice were fed ad libitum on a chow diet, and water extract of finger was orally administrated every other day for four weeks at two different concentractions (50 and 500 mg/kg B.W./day). In vitro study, the splenocytes proliferation was increased when water extract was supplemented in the range of 50-500 $\mu$l/ml concentration. In case of cytokines production, IL-1 $\beta$, IL-6 and TNF-$\alpha$ released by activated peritoneal macrophages were augmented by the supplementation of water extract of the Ginger. Ex vivo experiment, the highest proliferation of splenocytes and production of cytokines by activated peritoneal macrophages were seen in the mice orally administrated at the concentration of 500 mg/kg B.W./day. In conclusion, this study suggests that Ginger extracts may enhance the immune function by regulating the splenocytes proliferation and enhancing the cytokine prodution capacity by activated macrophages in mice.

• 동의생리병리학회지
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• 제32권2호
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• pp.99-105
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• 2018

The aim of this study is to compare the anti-inflammatory and immunological activity of different parts (bone, meat, and rind) of Yeonsan Ogye (YO). In order to evaluate cytotoxicity, MTT assay was performed. We investigated the production of nitric oxide (NO) and pro-inflammatory cytokines, such as IL-$1{\beta}$, IL-6, and TNF-${\alpha}$, in LPS-induced RAW264.7 cells. All parts of the YO showed no toxicity at concentrations of 1, 10, and $100{\mu}g/m{\ell}$. Rooster's bone, hen's bone, and rind decreased the production of NO. And rooster's bone, meat, and hen's bone also attenuated TNF-${\alpha}$ production in LPS-induced RAW 264.7 cells. In addition, all parts of the YO decreased IL-$1{\beta}$ and IL-6 production in LPS-induced RAW264.7 cells, whereas they all increased IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ production in normal RAW264.7 cells. Rooster exhibited higher immune activation and inhibitory activity on inflammation than a hen, and among different parts of the YO, bone showed the highest activity. Our results demonstrated and compared the anti-inflammatory and immunological activity of different parts of the YO. These results suggest that YO may be developed as a raw material for new health supplement food and medicine to attenuate various symptoms related to inflammation and immunity.

• Advances in Traditional Medicine
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• 제5권3호
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• pp.188-194
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• 2005

The Angelicae dahuricae radix (ADR) has been used a traditional medicine to treat acne, erythema, headache, toothache, sinusitis, colds, and flu in Korea, Japan and China. Here, we report the effect of ADR on compound 48/80-induced ear-swelling and the phorbol myristate acetate (PMA) plus calcium ionophore A23187-induced inflammatory cytokine secretion in the human mast cell line, HMC-1. ADR dose-dependently inhibited the ear-swelling response induced by intradermal injection of compound 48/80, In vitro model, PMA plus A23187 significantly increased interleukin $(IL)-1{\beta}$, IL-8, granulocyte macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor $(TNF)-{\alpha}$ secretion compared with media control. We also show that the increased cytokines $IL-1{\beta}$, IL-8, GM-CSF, and $TNF-{\alpha}$ level was significantly inhibited by treatment of ADR. In addition, ADR partially blocked PMA plus A23187-induced extracelluar signal-regulated kinases phosphorylation. These results suggest that ADR might explain its beneficial effect in the treatment of mast cell-mediated inflammatory diseases.

• 대한한방부인과학회지
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• 제23권3호
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• pp.91-100
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• 2010

Purpose: The purpose of this study was to investigate the effects of Prunellae Spica Water Extract(PSE) on immune response in macrophage cells. Methods: We had devided two group the one is normal group; not treated with PSE, and the other is experimental group; treated with PSE. We measured the cell viability of PSE on RAW 264.7 cells and investigated production of nitric oxide(NO) and cytokines such as interleukin(IL)-$1{\beta}$, IL-6 and tumor necrosis factor (TNF)-$\alpha$ with sample PSE. Results: 1. Cell viability of PSE on RAW 264.7 cells was significantly decreased in both 24 hr and 48 hr incubation. 2. NO production of PSE on RAW 264.7 cells was significantly increased in both 24 hr and 48 hr incubation. 3. IL-$1{\beta}$ production of PSE on RAW 264.7 cells was significantly increased under concentration over $50\;{\mu}g/m{\ell}$ in 24 hr incubation. 4. IL-6 production of PSE on RAW 264.7 cells was significantly increased under concentration over $50\;{\mu}g/m{\ell}$ in 24 hr incubation. 5. TNF-$\alpha$ production of PSE on RAW 264.7 cells was significantly increased under concentration over $50\;{\mu}g/m{\ell}$ in 24 hr incubation. Conclusion: NO, IL-$1{\beta}$, IL-6 and TNF-$\alpha$ production of PSE on RAW 264.7 cells was significantly increased. This study suggest that PSE stimulates the macrophage and enhances the immune response.

• 대한한방부인과학회지
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• 제25권2호
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• pp.12-22
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• 2012

Objectives: The aim of this study is to investigate immune enhancing effect of Houttuyniae Herba water extract(HW) on RAW 264.7 cell of mouse macrophages. Methods: Effects of HW on productions of nitric oxide(NO) and hydrogen peroxide($H_2O_2$) in RAW 264.7 mouse macrophages were measured. Effect of HW on production of cytokines such as interleukin(IL)-$1{\beta}$, IL-6, and tumor necrosis factor(TNF)-${\alpha}$ in RAW 264.7 cells was accessed by a multiplex bead array assay based on xMAP technology. All of results were represented P<0.05 compared to the normal. Results: 1. After 24 hr incubation, HW increased significantly NO production in RAW 264.7 cells at the concentrations of 25, 50, 100 and 200 ${\mu}g$/mL. 2. After 24 hr incubation, HW increased significantly hydrogen peroxide production in RAW 264.7 cells at the concentrations of 25, 50, 100 and 200 ${\mu}g$/mL. 3. After 24 hr incubation, HW increased significantly IL-$1{\beta}$ production in RAW 264.7 cells at the concentrations of 100 and 200 ${\mu}g$/mL. 4. After 24 hr incubation, HW increased significantly IL-6 production in RAW 264.7 cells at the concentrations of 100 and 200 ${\mu}g$/mL. 5. After 24 hr incubation, HW increased significantly TNF-${\alpha}$ production in RAW 264.7 cells at the concentrations of 50, 100, and 200 ${\mu}g$/mL. Conclusions: These results suggest that HW has immune enhancing activity related with its increasement of NO, hydrogen peroxide, IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ in macrophages.

• Journal of Microbiology and Biotechnology
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• 제9권6호
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• pp.826-831
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• 1999

${\beta}-Glucan$, one of the major cell wall components of Saccharomyces cerevisiae, is known to enhance the immune function, especially by activating macrophages. Accordingly, in an effort to develop a safe and efficient immune stimulatory agent, we prepared crude ${\beta}-glucan$ (glucan-p1) and partially purified ${\beta}-glucan$ that was free of mannoproteins (glucan-p2), and evaluated their effect on both the macrophage function and resistance to E. coli-induced peritonitis. To investigate the function of the macrophages, phagocytosis, $TNF-{\alpha}$ secretion, oxygen burst, and the expression of cytokine genes such as $IFN-{\gamma}$ and IL-12 were analyzed. Glucan-p2 markedly stimulated the macrophages with all these parameters. Glucan-p1, however, did not stimulate phagocytosis, yet it induced $TNF-{\alpha}$ secretion, oxygen burst, and the expression of $IFN-{\gamma}$ and IL-12, although less efficiently than glucan-p2. Finally, to test the in vivo protective effect of {\beta}-glucan against infection, the survival of mice from E. coli-induced peritonitis was investigated. After 24 h of the peritoneal challenge of E. coli, all of the mice treated with glucan-p2 survived whereas none survived in the control group. Glucan-p1 showed only a marginal effect in protecting the mice. These results suggest that mannoprotein-free gluean-p2, but not gluean-p1, can serve as an effective immune-stimulating agent.

• Tuberculosis and Respiratory Diseases
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• 제62권2호
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• pp.105-112
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• 2007

연구배경: 내독소로 유발된 급성폐손상의 발생기 전에 산화스트레스가 중요한 역할은 한다. 본 실험은 LPS로 유발한 급성폐손상 모델에서 항산화제인 ${\alpha}$-lipoic acid의 치료효과를 보고하였다. 방 법: Sprague-Dawley 쥐를 대상으로 LPS(E.coli, 3mg/Kg)를 기도내 주입 후 ${\alpha}$-lipoic acid를 복강 내 주입하였다. 2시간, 6시간 후에 폐포세척액에서 호중구수, CINC, 시토카인의 농도를 구하고 폐조직에서 MPO를 측정하였다. 결 과: ${\alpha}$-lipoic acid를 후처치한 군에서 LPS 단독군보다 2시간 뒤와 6시간 뒤에 총 세포수와 호중구의 수가 감소하였으나 단백질 농도는 차이가 없었다. 또한 염증성 인자인 TNF-${\alpha}$, IL-$1{\beta}$, IL-6의 농도도 ${\alpha}$-lipoic acid 처치군에서 유의한 감소를 보이지 못하였다. 결 론: LPS 로 급성폐손상 유도 모델에서 ${\alpha}$-lipoic acid의 후처치는 폐장내로의 호중구의 침윤은 억제할 수 있지만 급성폐손상을 약화시키지는 못 하였다.

• 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.