• 셀메드
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• 제2권3호
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• pp.27.1-27.6
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• 2012

Red ginseng, which has a variety of biological and pharmacological activities including antioxidant, anti-inflammatory, antimutagenic and anticarcinogenic effects, has been used for thousands of years as a general tonic in traditional oriental medicine. Here, we tested the immune regulatory activities of hydrolyzed red ginseng by malted barley (HRG) on the expressions of receptor interacting proteins (Rip) 2 and $I{\kappa}B$ kinase-beta (IKK-${\beta}$) in mouse peritoneal macrophages. We show that HRG increased the activations of Rip 2 and IKK-${\beta}$ for the first time. When HRG was used in combination with recombinant interferon-${\gamma}$ (rIFN-${\gamma}$), there was a marked cooperative induction of nitric oxide (NO) production. The increased expression of inducible NO synthase from rIFN-${\gamma}$ plus HRG-stimulated cells was almost completely inhibited by pre-treatment with pyrrolidine dithiocarbamate (PDTC), an inhibitor of nuclear factor-${\kappa}B$ (NF-${\kappa}B$). In addition, the treatment of peritoneal macrophages with rIFN-${\gamma}$ plus HRG caused significant increases in tumor necrosis factor (TNF)-${\alpha}$ mRNA expression and production. Because NO and TNF-${\alpha}$ play an important role in the immune function and host defense, HRG treatment can modulate several aspects of the host defense mechanisms as a result of the stimulations of the inducible nitric oxide synthase and NF-${\kappa}B$. In conclusion, our findings demonstrate that HRG increases the productions of NO and TNF-${\alpha}$ from rIFN-${\gamma}$-primed macrophages and suggest that Rip2/IKK-${\beta}$ plays a critical role in mediating these immune regulatory effects of HRG.

• 대한한방소아과학회지
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• 제20권1호
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• pp.15-29
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• 2006

Objective : Based on the Th1/Th2 inbalance hypothesis, we aimed to evaluate the effects of NaesowhajungtongGamibang on serum $interferon{\gamma}$, interleukin-4, interleukin-5, of 19 patients with atopic dermatitis. Materials & Methods: The subjects are consisted of 19 patients with atopic dermatitis, and had been treated with NaesowhajungtongGamibang decoction for 45 days. Serum $IFN-{\gamma}$, IL-4, IL-5 level were checked before and 45 days after treatments. Results: The serum $IFN-{\gamma}$, IL-5, level in patients with atopic dermatitis were slightly decreased compared with normal control group, but had no statistical significance. The serum IL-4, level in patients with atopic dermatitis was slightly increased compared with normal control group, but had no statistical significance. After treatment with NaesowhajungtongGamibang for 45 days, serum $IFN-{\gamma}$, IL-5, level were increased, but had no statistical significance. After treatment with NaesowhajungtongGamibang for 45 days, serum IL-4 level were decreased, but had no statistical significance. Conclusion: This study shows that NaesowhajungtongGamibang decoction had effects were not correspond with Th1/Th2 inbalance hypothesis. Therefore study for other mechanism of NaesowhajungtongGamibang on atopic dermatitis is required.

• The Korean Journal of Physiology and Pharmacology
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• 제5권6호
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• pp.521-527
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• 2001

Diclofenac, a phenylacetic acid derivative, is a widely used non-steroidal anti-inflammatory drug (NSAID) to provide effective relief of inflammation and pain. Nitric oxide (NO) synthesized by inducible nitric oxide synthase (iNOS) has been implicated as a mediator of inflammation. We examined the inhibitory effects of diclofenac on the induction of iNOS in RAW 264.7 macrophages which were activated with lipopolysaccharide (LPS) plus interferon-gamma $(IFN-{\gamma}).$ Treatment of RAW 264.7 cells with diclofenac and other NSAIDs (aspirin and indomethacin) significantly inhibited NO production and iNOS protein expression induced by LPS plus $IFN-{\gamma}.$ Also, diclofenac but not aspirin and indomethacin, inhibited iNOS mRNA expression and nuclear factor-kappa B $(NF-{\kappa}B)$ binding activity concentration-dependently. Furthermore, transfection of RAW 264.7 cells with iNOS promoter linked to a CAT reporter gene revealed that only diclofenac inhibited the iNOS promoter activity induced by LPS plus $IFN-{\gamma}$ through the $NF-{\kappa}B$ sites of iNOS promoter. Taken together, these suggest that diclofenac may exert its anti-inflammatory effect by inhibiting iNOS gene expression at the transcriptional level through suppression of $NF-{\kappa}B$ activation.

• 동의생리병리학회지
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• 제21권4호
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• pp.1017-1024
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• 2007

Thymus and activation-regulated chemokine (TARC/CCL-17), produced by keratinocytes, is a CC chemokine known to selectively Th2 type T cells via $CCR4^+$ and is implicated in the development of atopic dermatitis (AD). TARC/CCL17 expression was induced by cytokines such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interferon-${\gamma}$ (IFN-${\gamma}$). We recently found that the wogonin, a flavone isolated from Scutellaria baicalensis, suppressed TARC expression via heme oxygenase 1 (HO1) in human keratinocytes induced with mite antigen. However, little is known about the inhibitory mechanism of wogonin on TARC/CCL-17 expression stimulated with cytokines. To investigate the inhibitory mechanism, I determined the inhibitory effects of wogonin on the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and $I{\kappa}B{\alpha}$ phosphorylation, and also examined the activation of p38 MAP kainase in HaCaT keratinocytes stimulated with TNF-${\alpha}$ and IFN-${\gamma}$. Wogonin inhibited NF-${\kappa}B$-DNA complex, NF-${\kappa}B$ binding activity, and the phosphorylation of $I{\kappa}B{\alpha}$ in a dose dependent manner. Wogonin also inhibited the translocation of NF-${\kappa}B$ from cytosol to nucleus. Moreover, the phosphorylation of of p38 MAP kinase in the TNF-${\alpha}$ and IFN-${\gamma}$-stimulated HaCaT keratinocytes were suppressed by wogonin in a dose dependent manner. These results suggest that wogonin may inhibit cytokine-induced NF-${\kappa}B$ activation by $I{\kappa}B{\alpha}$ degradation via suppression of p38 MAP kinase signaling pathway in keratinocytes and modulation of wogonin signaling pathway may be beneficial for the treatment of AD.

• Parasites, Hosts and Diseases
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• 제51권1호
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• pp.133-137
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• 2013

This study aimed to measure the levels of interferon-gamma (IFN-${\gamma}$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate ($NO_x$) in serum of dogs experimentally infected with Rangelia vitalii. Twelve female mongrel dogs were divided into 2 groups; group A (uninfected controls) composed by healthy dogs (n=5) and group B consisting of dogs inoculated with R. vitalii (n=7). Animals were monitored by blood smear examinations, which showed intraerythrocytic forms of the parasite on day 5 post-infection (PI). Blood samples were collected through the jugular vein on days 0, 10, and 20 PI to determine the serum levels of IFN-${\gamma}$, TNF-${\alpha}$, IL-1, IL-6, and $NO_x$. Cytokines were assessed by ELISA quantitative sandwich technique, and $NO_x$ was measured by the modified Griess method. Cytokine levels (IFN-${\gamma}$, TNF-${\alpha}$, IL-1, and IL-6) were increased (P<0.01) in serum of infected animals. Serum levels of $NO_x$ were also increased on days 10 PI (P<0.01) and 20 PI (P<0.05) in infected animals. Therefore, the infection with R. vitalii causes an increase in proinflammatory cytokines and nitric oxide content. These alterations may be associated with host immune protection against the parasite.

• 한국식품과학회지
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• 제45권3호
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• pp.385-390
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• 2013

본 연구에서는 참치 추출물 및 분획물들에 의한 NO 생성에 미치는 영향을 살펴보았고 참치 85% aq. MeOH 분획물을 중심으로 면역과정의 생물학적 작용과 대사적 변화를 유도하는 IL-6, IFN-${\gamma}$ 및 TNF-${\alpha}$ 같은 사이토카인의 생성을 측정하여 참치 추출물에 의한 면역 기능 조절에 대하여 검토하였다. 참치 추출물과 각 분획물들은 control보다 낮은 NO 생성량을 나타내었으며, 특히 85% aq. MeOH 및 n-hexane 분획물에 의한 저해효과가 높았다. IL-6와 TNF-${\alpha}$의 경우, 참치 85% aq. MeOH 분획물을 농도별(1, 3 및 $10{\mu}g$)로 처리했을 때 그 중 $10{\mu}g/mL$ 첨가농도에서 6시간 배양 후 가장 낮은 IL-6 및 TNF-${\alpha}$ 생성량을 확인할 수가 있었다(p<0.05). IFN-${\gamma}$의 생성은 참치 85% aq. MeOH 분획물(1, $3{\mu}g/mLg$ 첨가농도)을 LPS와 함께 처리 했을 때 24시간과 48시간 배양 시 생성량이 증가하는 경향이었으나 유의적 차이는 없었다. 따라서 참치 85% aq. MeOH 분획물은 NO 생성과 pro-inflammatory 사이토카인(IL-6와 TNF-${\alpha}$)을 감소시켜 염증반응을 예방할 것으로 기대된다.

• Tuberculosis and Respiratory Diseases
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• 제42권5호
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• pp.703-712
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• 1995

연구배경: 말초혈액 단핵구는 정상적인 면역반응에 중요한 세포로서 탐식 기능과 항원 제공 기능외에 다양한 종류의 Cytokine을 생성하며, 이중 IL-8은 호중구에 대한 강력한 주화 작용과 직접적인 활성화 작용 등을 통해서 염증 작용을 증폭시키는 역할을 하는 것으로 알려져 었다. 따라서 IL-8 작용의 억제를 통하여 항염 효과를 기대할 수 있으며, 이러한 작용을 나타낼 것으로 기대되는 Dexamethasone, $PGE_2$, Indomethacin 및 IFN-$\gamma$를 이용하여 이러한 약제들이 말초혈액 단핵구에서 내독소 자극에 의한 IL-8의 생성 자극 효과에 어떤 영향을 미치는 지에 대해서 알아보았다. 방법: 말초혈액 단핵구는 자원자에게서 채취한 혈액을 Ficoll Hypaque density gradient method에 의해서 백혈구 층을 분리한 뒤에 플라스틱 접시에 부착함으로써 분리하였다. Dexamethasone, $PGE_2$, Indomethacin은 내독소로 자극하기 한 시간 전, 후에 처치하였고, IFN-$\gamma$는 내독소로 자극하기 한 시간 전에만 전처치 하였다. 내독소로 자극한 뒤 4시간 뒤에 RNA를 extraction한 뒤 Northern blot analysis를 시행하여 IL-8 mRNA를 분석하였고, 24시간 뒤에 ELISA를 통하여 IL-8 단백을 정량하였다. 이 과정을 3회 반복하여 다음과 같은 결과를 얻었다. 결과: 1) Dexamethasone의 전, 후 처치는 내독소 자극에 의한 IL-8 mRNA와 단백의 생성을 감소시켰다. 2) IFN-$\gamma$의 단독 투여는 내독소 자극을 받지 않은 군에서 IL-8 mRNA와 단백의 생성을 감소시켰다. 3) 내독소 투여 전에 IFN-$\gamma$를 전 처치 하였을 때, 내독소 단독 투여군에 비해 IL-8 mRNA 발현은 감소하였으나 IL-8 단백의 분비에는 차이가 없었다. 4) $PGE_2$와 Indomethacin은 각각 사용한 농도($10^{-6}M$, $10{\mu}M$)에서는 내독소 자극에 의한 IL-8 mRNA 및 단백의 생성에 별다른 영향을 미치지 못하였다. 결론: Dexamethasone은 말초혈액 단핵구에서 내독소의 자극에 의한 IL-8 mRNA 발현 및 단백의 생성을 억제함으로써 염증 반응을 억제할 것으로 기대된다.

• Clinical and Experimental Reproductive Medicine
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• 제37권2호
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• pp.125-134
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• 2010

목 적: 난관수종액내의 사이토카인 농도를 측정하고, 사이토카인 농도가 다른 난관수종액을 이용하여 생쥐 배아 발생에 미치는 영향을 비교하고자 하였다. 연구방법: 난관수종액은 자궁난관 조영술에서 난관수종이 진단되어 복강경을 통한 난관 절제술을 시행하는 경우 난관 절제술 전에 난관으로부터 채취한 다음 3,000 rpm에서 10분간 원심분리시킨 후 상층액만을 $-20^{\circ}C$에서 보관하였다. 난관수종액의 사이토카인의 조성 및 농도를 확인하기 위하여 interleukin (IL)-$1{\alpha}$, IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-$\alpha$, interferon (IFN)-$\gamma$, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), monocyte chemotactic protein (MCP)-1 등을 ELISA 방법으로 측정하였다. 기본 배양액에 난관수종액을 5%, 10%, 30%의 비율로 첨가하여 각 군별로 배반포로의 발달을 관찰하였다. 결 과: 난관수종액내에서 IL-$1{\alpha}$, IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-$\alpha$, IFN-$\gamma$, VEGF, EGF, MCP-1가 검출되었으며, 그 농도에 있어서는 큰 차이를 보였다. 정상 혈청 농도에 비하여 난관수종액-1은 IL-6, IL-10이 증가되어 있었고, 난관 수종액-2는 IFN-$\gamma$, MCP-1 및 VEGF가 증가되어 있었다. 각 난관수종액의 Th1/Th2 비는 HSF-1의 경우 IFN-$\gamma$:IL-10이 3.69로 정상인 데 비하여 HSF-2의 경우 IFN-$\gamma$:IL-10이 61.14로 크게 증가되어 있었다. 난관수종액을 포함하지 않는 배양액에서는 배반포기 발달률은 76.7%이었고, 난관수종액-1군은 74%로 대조군과 차이를 보이지 않았지만, 난관수종액-2군의 경우 27.7%로서 대조군 및 난관수종액-1군과도 유의한 차이를 보였다. 난관수종액-1의 경우 난관수종액 농도에 따른 차이는 없었으며, 난관수종액-2군의 경우 농도에 증가함에 따라 배반포로의 발달이 감소하기는 하였지만 통계적으로 유의하지는 않았다. 결 론: 난관수종액마다 사이토카인의 조성이 다르며 이에 따라 생쥐 배아발달에 미치는 영향이 다를 수 있다. 염증성 사이토카인이 증가된 난관수종액이 배아발달에 악영향을 미칠 것으로 추정된다. 특정 사이토카인에 의한 작용을 규명하기는 위해서는 향후 지속적인 연구가 필요할 것으로 생각된다.

• Advances in Traditional Medicine
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• 제2권1호
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• pp.41-46
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• 2002

In our study, the several cytokines were determined in phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of Adamantiades-Behcets patients. Adamantiades-Behcets disease (ABD) is a systemic inflammatory disorder and might involve immune dysfunction. High levels of $TNF-\alpha,\;IL-1\beta$ and $IFN-{\gamma}$ indicate the activation of inflammatory reactions and immune system in ABD. Gami-Phedoc-San (GPS) is an Oriental herbal medication, which has been used in Korea for the treatment of ABD. GPS (1 mg/ ml) significantly inhibited the secretion of proinflammatory cytokines, $TNF-\alpha\;and\;IL-1\beta$, compared to absence of GPS (by $50.5{\pm}1.9%$ inhibition for $TNF-\alpha$ and $106.9{\pm}16.8%$ for $IL-1\beta$). GPS also inhibited the production of $IFN-\gamma$, immunoregulatory Th1 cytokine, by $78.4{\pm}2.8%$. The inhibitory effects of GPS on cytokine secretion showed dose-dependent manner, and the pre-treatment of 1 mg/ml GPS had better effects than immunosuppressive drug for treatment of ABD, cyclosporin A. Our results suggest that GPS treatment for ABD patients might have pharmacological activity of immune and inflammatory responses through the cytokine modulation.

• Archives of Pharmacal Research
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• 제19권5호
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• pp.368-373
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• 1996

Nitric oxide (NO) is synthesized by various cells involved in inflammatory reactions and may then act on mast cells. In the present work, we attempted to clarify the role of this molecule on the proliferation of mouse bone marrow derived-mast cells (BMMC). Swiss 3T3 fibroblastsproduced nitrite ($NO_{2}$) and nitrate ($NO_{3}$) upon treatment with interferon ${\gamma}$(IFN-${\gamma}$). This formation was dependent of L-arginine and could be inhibited by the -L-arginine analogue $N^{G}$-monomethyl-L-arginine ($N^{G}$MMA). The effect of IFN-g was drastically invreased by cotreatment with tumor necrosis factor g(IFN-g). BMMC were maintained in vitro for as long as 30 days when cocultured with Swiss 3T3 fibroblasts. coculture with $N^{G}$MMA, significantly increased the number of BMMC. These results indicate that NO involves the inhibition of proliferation of BMMC when cocultured with Swiss 3T3 fibroblasts.