• IMMUNE NETWORK
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• 제1권3호
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• pp.250-259
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• 2001

To determine if initial infection with Mycobacterium tuberculosis changes the balance of cytokines between T cells and macrophages, we evaluated interferon (IFN)-${\gamma}$), interleukin-12 (IL)-12, and tumor necrosis factor (TNF)-${\alpha}$ productions by peripheral blood mononuclear cells (PBMC) from 15 untreated active pulmonary tuberculosis (TB) patients and 12 healthy tuberculin reactors (HTR). Freshly isolated PBMC were stimulated with Triton X-100 solubilized protein (TSP), 30-kDa or purified protein derivatives (PPD) antigen for 6, 18 and 96 hours. IL-12 p40 production by antigen-stimulated PBMC from TB patients was significantly decreased compared with that in HTR. In addition, IFN-${\gamma}$ production was significantly depressed in TB patients than that in HTR at a 96-hr stimulation. However, TNF-${\alpha}$ production was significantly higher in antigen-stimulated PBMC from TB than that of HTR. A pronounced increase in IFN-${\gamma}$ protein followed neutralization of IL-10 in early TB patients. However, neutralization of TNF-${\alpha}$ did not significantly alter IFN-${\gamma}$ induction in PBMC from TB patients. There were no significantly differences in the cytokine productions among three proteins, TSP, 30-kDa or PPD antigen. These results indicate that development of TB may be strongly associated with dysregulated productions of IL-12, IFN-${\gamma}$ and TNF-${\alpha}$, during the initial immune responses to M. tuberculosis. Further understanding of operative cytokine networks during human immune cell responses to protein antigens of M. tuberculosis may improve strategies for vaccine development.

• 대한본초학회지
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• 제25권2호
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• pp.129-136
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• 2010

Objective : Sinapis alba L. (SA) is a korean traditional herbal medicine that is usually used to prevent or treat inflammatory diseases, such as respiratory infection and rheumatoid arthritis. However, the effects of SA supplementation in vitro on serum antibody levels, splenocyte and peritoneal macrophage immune responses have not yet been determined. In this study, we examined the effect of SA on the production of Th1/Th2 cytokines. Methods : Splenocytes were isolated from naive C57BL/6 mice. Cells were enriched for CD4+ cell populations by first staining the cells with anti-CD4 (BD PharMingen, Calif, USA). CD4+ T cells were selected on a (CS) column, and the flow-through was collected as CD4+ T cells. Isolated cells were activated by overnight incubation on 24-well plates coated with $1{\mu}g/mL$ anti-CD3, $1{\mu}g/mL$ anti-CD28 and with SA ($100{\mu}g/mL$). Primary macrophages were collected from the peritoneal cavities of mice (8-week-old female C57BL/6). The peritoneal macrophages were washed and plated with RPMI-1640 overnight for the experiments. After 48-hours cultures, samples were centrifuged at 2000 rpm for 10 minutes, and the supernatants were stored at $-80^{\circ}C$. Mouse IL-4, IFN-$\gamma$ and TNF-$\alpha$ were quantified using ELISA kits (BioSource International, Camarillo, Calif, USA) according to the manufacturer's protocols. Results : SA at 100ug/ml decreased the generation of Th1 cytokine (IFN-$\gamma$) by 0.5-fold. However, SA has no effect on Th2 (IL-4) production. Conclusions : These results suggest that SA may play an important role in the control of T-cell-mediated autoimmunity by down-regulation of Th1 cytokine (especially IFN-$\gamma$, TNF-$\alpha$). These data may contribute to the design of new immunomodulating treatments for a group of autoimmune diseases.

• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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• pp.117-124
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• 2017

The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-${\alpha}$, interferon (IFN)-${\gamma}$, and interleukin (IL)-$1{\beta}$] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-${\alpha}$; 5 ng/ml, IFN-${\gamma}$; 5 ng/ml, and IL-$1{\beta}$; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), attenuates cytokine mixture (TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.

• IMMUNE NETWORK
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• 제8권3호
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• pp.98-105
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• 2008

Background: Allergic inflammation was induced by activated Th2 lymphocytes, leading to IgE production and eosinophil activation. A Th2 disproportion was shown in atopic children soon after birth. During specific allergen stimulation, an increase of Th2 cells was observed in most cases. In this study, we prepared new screening "whole blood" system for searching the anti-atopic materials. Cytokine production and IgE secretion from whole blood system were assessed and we confirmed the results by using animal system. Methods: Pathological features in NC/Nga mice are similar to those observed in human atopic dermatitis. Whole blood from NC/Nga mouse was stimulated by using TNCB (Th2 activator) or candidate materials of anti-atopic dermatitis, and the production of cytokines (IL-4, IL-12, and IFN-${\gamma}$) were measured by ELISA. In order to confirm the results of whole blood system, in vivo test was done by using NC/Nga mice. Results: In whole blood system, LPS and extracts of green tea, hardy orange and onion induced the production of IL-12 and IFN-${\gamma}$ while they reduced the production of IL-4. Also, LPS and extracts of onion reduced IgE production. Though atopic dermatitis was observed from a mouse stimulated with TNCB, it was not when a mouse was co-stimulated in LPS or extracts of onion. The results are same as those observed in whole blood system. Conclusion: Whole blood system was simple and speedy methods for searching a materials compared with the conventional high-cost animal system. And the results using whole blood system was proved to be reliable in our experiments for screening anti-atopic material. We expect that the system can be applied to other experiments for searching similar materials.

• 사상체질의학회지
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• 제15권2호
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• pp.166-179
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• 2003

In order to evaluate the antiallergic effects of CSYJT, studies were done. We measured the cytotoxic activity for cytokines transcript expression, production of IL-4, IgE, $IFN-{\gamma}$, proliferation of B cell in HRF plus anti-CD40mAb plus rIL-4 stimulated murine splenic B cells. and cytokines transcript expression of IgE in Mast cell The results were obtained as follows: 1. CSYJT decreased the expression of IL-4 in mast cell significantly. 2. CSYJT decreased the production of IL-4 significantly. 3. CSYJT decreased the expression of IgE in mast cell significantly. 4. CSYJT decreased the production of IgE significantly. 5. CSYJT increased the appearance of $IFN-{\gamma}$. The facts above prove that CSYJT is effective against the allergy. Thus, I think that we should study on this continuously.

• Advances in Traditional Medicine
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• 제2권2호
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• pp.113-118
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• 2002

Falun Gong (FG) is an advanced system of cultivation and practice, which is beneficial for both mind and body. In this study we investigated the effects of FG on the production of cytokines in FG practitioner (FGP). To study whether plasma cytokines levels were affected by FG, their levels were analyzed. The amount of $interferon-{\gamma}$ $(IFN-{\gamma})$, interleukin (IL)-2, IL-4 and IL-6 (2.5-fold for $IFN-{\gamma}$, 1.2-fold for IL-2, 2.1-fold for IL-4 and 2.5-fold for IL-6, respectively) were significantly higher in the FGP group than normal group (P<0.05). Peripheral blood mononuclear cells obtained from normal healthy control and FGP were cultured for 24 h in the presence or absence of lipopolysaccharide. The amount of $IFN-{\gamma}$, IL-2, IL-4 and IL-6 in culture supernatant was quantified. However, there were no significant differences in the level of the same cytokines between the normal and FGP group. These data suggest that FG cultivation may contribute to immune-enhancement in vivo.

• Molecular & Cellular Toxicology
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• 제1권3호
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• pp.196-202
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• 2005

Nitric oxide (NO) is a small, diffusible, and highly reactive molecule, which plays dichotomous regulatory roles under physiological and pathological conditions. NO promotes apoptosis in some cells, and inhibits apoptosis in other cells. In the present study, we attempted to characterize the NO signaling pathway and cellular response in PC12 cells treated with cytokines. $IFN{\gamma}\;and\;TNF{\alpha}$ treatment resulted in a synergistic increase of nitrite accumulation, with the induction of inducible nitric oxide synthase (iNOS) in the PC12 cells. Moreover, as nitrite concentration increased, cell viability decreased. In order to explore MAP kinase involvement in nitric oxide production resultant from $IFN{\gamma}\;and\;TNF{\alpha}$ stimulation, we measured the activation of MAP kinase using specific MAP kinase inhibitors. PC12 cells pretreated with SB203580, a p38 MAP kinase-specific inhibitor, resulted in the inhibition of iNOS expression and NO production. However, PD98059, an ERK/MAP kinase-specific inhibitor, was not observed to exert such an effect. In addition, Stat1 activated by $IFN{\gamma}\;and\;TNF{\alpha}$ was interacted with p38 MAPK. These data suggest that p38 MAP kinase mediates cytokine-mediated iNOS expression in the PC12 cells, and Jak/Stat pathway interferes with p38 MAPK signaling pathway.

• 대한한방소아과학회지
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• 제19권1호
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• pp.35-52
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• 2005

Objectives : Conclusion : The purpose of this study is to examine effect that KDKEJ used to atopic dermatitis disease patient get in atopy eruption control experimentally. Methods : We analyzed the expression of IgE, IL-6, II-4, IL-5 and IL-13's level in serum, and $IFN-{\gamma}'$ production by KDKEJ extract. We also analyzed KDKEJ extract get to NC/Nga mine's skin establishment analyzes neck-back skin after biopsy, and H&E method measured about epidermis and dermis part in comparison with control group. Results : In this research KDKEJ extract as treatment result to a NC/Nga mice, IgE and IL-6 content in serum decreased remarkably than control group. And decreased than result control group which measure II-4, IL-5 and IL-13's level in serum and $IFN-{\gamma}'$ production secreted in Th1 cell displayed increase by KDKEJ extract. IL-4 and $IFN-{\gamma}'$ gene revelation amount displayed marked decrease than control group in result that observe effect that get in skin of a NC/Nga mice's skin establishment analyzes neck-back skin after biposy, and dye by H&E method decreased about epidermis and inflammation of dermis part remarkable than control group. Conclusions : These results suggest that Th1 cell and Th2 cell observe to be shifted by secretion amount of IL-4 and $IFN-{\gamma}$ by KDKEJ extract could know that KDKEJ extract can use usefully in allergy autoimmune disease.

• 한국식품과학회지
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• 제36권6호
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• pp.986-990
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• 2004

대식세포는 IL-1, IL-6, $TNF-{\alpha},\;IFN-{\gamma}$의 중요한 근원이고, 전염성의 병원체와 종양 세포에 대해 저항하는 주요한 effector 세포이다. 이것은 cytokine signal에 의해 세포파괴가 되도록 활성화 된다. 이번 연구에서 우리는 산더덕의 물 추출물이 cytokine, nitric oxide와 같은 effector 분자를 유도하기 위해 대식세포를 활성화하는지를 알아보기 위하여 실험하였다. 산더덕 추출물에 의한 대식세포의 NO 생성은 농도 의존적이고, 시간 의존적이었다. iNOS는 시간이 지날수록 발현이 유도되었다. 산더덕 추출물에 의한 IL-1과 IL-6 mRNA 유도는 시간 의존적으로 증가 되었고, 처리 후 24시간에 최고점에 도달하였다. 이것은 활성화된 대식세포가 종양세포를 죽일 수 있음을 말한다. $TNF-{\alpha}\;mRNA$의 양은 시간이 지나도 일정하였고, $IFN-{\gamma}\;mRNA$의 양은 산더덕 추출물의 처리 1시간 후에 빠르게 강화되었다. 이러한 결과로부터 산더덕은 효과적인 면역조절자이고 대식세포의 항종양활성을 강화함을 알 수 있다.

• 한국버섯학회지
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• 제11권2호
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• pp.92-98
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• 2013

본 연구는 식용버섯, 특히 능이버섯이 면역조절기능제로서의 가치 여부를 평가하기 위하여 수행되었다. 본 연구를 위해 능이버섯 및 잎새버섯, 표고버섯이 사용되었다. 버섯 추출물을 투여한 생쥐의 혈장내 IgG1 및 IgG2a 수준을 측정하였고, 비장 단일 세포군을 이용하여 T 림프구 및 B 림프구의 in vitro 활성화 결과 생성된 $IFN{\gamma}$와 IL-4 수준을 각각 분석하였다. 실험 결과 능이버섯 추출물 500 mg/kg BW 투여군과 잎새버섯 추출물 500 mg/kg BW을 투여한 군에서 각각 $IFN{\gamma}$/IL-4의 비가 다른 군에 비해 높은 경향을 보였다. 또한 혈장 내 IgG2a/IgG1의 비가 능이버섯 추출물 투여군의 경우에 다른 군보다 높았다. 이는 능이버섯이 항암작용 및 항바이러스 작용과 같은 type-1 반응을 촉진할 가능성이 있으며, 그 효과가 이미 입증된 표고버섯이나 잎새버섯과 비교하여 식용버섯으로써 면역조절 기능 강화 측면에서 우수한 버섯이라 사료된다.