• 한국식품과학회지
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• 제38권6호
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• pp.829-834
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• 2006

HIV 감염 후 AIDS로의 진행과정에서 cytokines의 변화는 필수적인 결과로서 나타나게 된다. 본 연구에서는 AIDS 동물모델을 사용하여 Pyc Cytokines발현에 미치는 영향과 조절 매개체로서 $NF-{\kappa}B$의 관련성 및 작용 기작 확인에 초점을 두었다. LP-BM5 retrovirus에 감염된 C57BL/6 생쥐를 이용하여12주간에 걸친 실험에서Pyc 투여는 Th1과 Th2 cytokines의 혈중농도를 조절하여 murine AIDS로의 진행을 억제하는 데 역할을 하는 것으로 사료된다. 특히 Th2 cytokines의 mRNA 발현을 억제함에 따라 Th1 cytokines의 혈중농도는 상대적으로 증가한 것으로 사료된다. 이러한 결과는 Pyc가 Th2 cytokines을 선택적으로 transcription level에서 조절하고 있음을 의미하고 있다. 또한 Th2 cytokines mRNA 발현 조절은 $NF-{\kappa}B$의 활성화에 의한 것으로 추정된다. 본 연구는 AIDS 동물모델에서 $NF-{\kappa}B$의 조절을 통한 cytokines의 발현 조절의 가능성을 제시함과 동시에 Pyc의 역할에 대해 자료를 제시하고 있다. 또한 향후 murine AIDS 진행 억제제로서의 Pyc의 기작에 대한 일면을 보인 것에 의의를 두고자 한다.

• Tuberculosis and Respiratory Diseases
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• 제49권3호
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• pp.332-342
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• 2000

연구배경 : 염증매개 사이토카인은 염증성 폐질환의 중요한 매개물질이다. 폐 상피세포는 염증세포에서 분비되는 사이토카인에 의해 interleukin, chemokines, colony stimulating factors와 growth factor등을 생산 및 분비함으로써 국소 염증 부위에서의 사이토카인 network에 중요한 역할을 한다. 따라서 폐 상피세포에서 염증매개 사이토카인의 발현 기전에 대한 이해는 염증성 폐질환의 기전규명과 이에 기초한 새로운 치료법의 개발에 생각된다. 대부분의 사이토카인은 NF-${\kappa}B$전사인자에 의해 발현되는데 폐 상피세포에서 염증매개 사이토키인의 발현과 NF-${\kappa}B/I{\kappa}B$ 경로와의 관련성에 관한 연구는 부족한 실정이다. 방법 : BEAS-2B, A549, NCI-H157, NCI-H719 세포에서 IL-1$\beta$와 TNF-$\alpha$ 자극에 의한 IL-8과 TNF-$\alpha$ mRNA의 발현 양상을 평가하였고 이들의 발현과 관찰하였고 NF-${\kappa}B/I{\kappa}B$ 경로와의 관련성을 평가하기 위하여 IL-l$\beta$와 TNF-$\alpha$ 자극에 의한 NF-${\kappa}B$의 활성화 및 $I{\kappa}B{\alpha}$와 $I{\kappa}B{\beta}$의 분해 양상을 관찰하였다. 폐 상피세포의 종류에 따른 NF-${\kappa}B/I{\kappa}B$ 경로 조절의 기전을 규명하고자 IL-1$\beta$와 TNF-$\alpha$ 자극에 의한 $I{\kappa}B{\alpha}$의 인산화와 기저상태에서 IKK$\alpha$의 발현을 평가하였다. 결과 : BEAS-2B, A549, NCI-H157 세포에서는 IL-1$\beta$와 TNF-$\alpha$ 자극으로 $I{\kappa}B{\alpha}$와 $I{\kappa}B{\beta}$가 분해되었고 NF-${\kappa}B$의 활성화가 관찰되었으며 IL-8과 TNF-$\alpha$mRNA의 발현이 유도되었다. NCI-H719 세포에서는 IL-1$\beta$와 TNF-$\alpha$ 자극으로 $I{\kappa}B$ 분해에 의한 NF-${\kappa}B$의 활성화 및 염증매개 사이토카인의 발현이 관찰되지 않았다. BEAS-2B, A549, NCI-H157 세포에서는 IL-1$\beta$와 TNF-$\alpha$ 자극으로 ${\kappa}B$의 인산화가 관찰되었지만 NCI-H719 세포에서는 관찰되지 않았다. 기저상태의 IKK$\alpha$ 발현은 세포간에 차이가 관찰되지 않았다. 결론 : 폐 상피세포에서 NF-${\kappa}B/I{\kappa}B$ 경로는 염증매개 사이토카인 발현에 매우 중요한 역할을 하고, 일부 세포에서는 NF-${\kappa}B/I{\kappa}B$ 경로 조절의 차이를 보이는데 이는 IKK보다 상위 단계의 세포내 신호전달체계의 이상에 기인한 것으로 생각된다.

• The Korean Journal of Physiology and Pharmacology
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• 제3권5호
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• pp.521-528
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• 1999

Reactive oxygen species (ROS), generated by infiltrating neutrophils, are considered as an important regulator in the pathogenesis and deveolpment of pancreatitis. The present study aims to investigate whether neutrophils primed by $4{\beta}-phorbol\;12{\beta}-myristate\;13{\alpha}-acetate$ (PMA) affect the productions $H_2O_2$ and lipid peroxide (LPO), $NF-_{\kappa}B$ activation and cytokine production in pancreatic acinar cells, and whether these alterations were inhibited by an antioxidant, N-acetylcysteine (NAC) and superoxide dismutase (SOD). $H_2O_2$ (ferrithiocyanate method), LPO (as thiobarbiturate reactive substances), and cytokines $(IL-l{\bata},\; IL-6,\;TNF-{\alpha};\;enzyme-linked\;immunosorbent\;assay)$ and $NF-_{\kappa}B$ activation (electrophoretic mobility shift assay) were analyzed in acinar cells treated with or without PMA-primed neutrophils in the absence or presence of NAC (10 mM) or SOD (300 U/ml). As a result, the productions of H2O2, LPO and $TNF-{\alpha}$ were increased with the ratio of PMA-primed neutrophils to acinar cells while the productions of LPO, $IL-l{\beta},\;IL-6\;and\;TNF-{\alpha}$ were increased with time. PMA-primed neutrophils resulted in the activation of $NF-_{\kappa}B.$ Both NAC and SOD inhibited neutrophil-induced alterations in acinar cells. In conclusion, ROS, generated by neutrophils, activates $NF-_{\kappa}B,$ resulting in upregulation of inflammatary cytokines in acinar cells. Antioxidants might be clinically useful antiinflammatory agents by inhibiting oxidant-mediated activation of $NF-_{\kappa}B$ and decreasing cytokine production.

• Molecules and Cells
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• 제37권3호
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• pp.189-195
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• 2014

The NF-${\kappa}B$ pathway transcriptionally controls a large set of target genes that play important roles in cell survival, inflammation, and immune responses. While many studies showed anti-tumorigenic and pro-survival role of NF-${\kappa}B$ in cancer cells, recent findings postulate that NF-${\kappa}B$ participates in a senescence-associated cytokine response, thereby suggesting a tumor restraining role of NF-${\kappa}B$. In this review, we discuss implications of the NF-${\kappa}B$ signaling pathway in cancer. Particularly, we emphasize the connection of NF-${\kappa}B$ with cellular senescence as a response to chemotherapy, and furthermore, present examples how distinct oncogenic network contexts surrounding NF-${\kappa}B$ produce fundamentally different treatment outcomes in aggressive B-cell lymphomas as an example.

• 대한한방부인과학회지
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• 제30권2호
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• pp.1-15
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• 2017

Objectives: The object of this study was to identify the anti-inflammatory effects of Patrinia scabiosaefolia aqueous extract (PSE). Methods: RAW 264.7 cells were pre-treated with PSE and then incubated with or without lipopolysaccharide (LPS). Cell viability, production of nitric oxide (NO), secretion of pro-inflammatory cytokine, activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-${\kappa}B$) were measured. In addition, we observed mice survival rate after LPS and their cytokine levels of serum. We also observed inflammatory and hemorrhagic change on the histological sections of the liver. Results: PSE inhibited LPS-induced NO production, interleukin (IL)-6 secretion, c-Jun NH2-terminal kinase (JNK) and NF-${\kappa}B$ activation. In addition, PSE reduced the death rate of LPS-induced mice and IL-6 production on the serum of mice. PSE inhibited inflammation and hemorrhage on liver tissue as well. Conclusions: The results suggest that PSE have anti-inflammatory effects by inhibited NF-${\kappa}B$ and JNK activation, IL-6 secretion, and NO production. So PSE may be effective treatment for the inflammatory disease.

• BMB Reports
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• 제48권3호
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• pp.172-177
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• 2015

Upregulation of pro-inflammatory mediators contributes to ${\beta}$-cell destruction and enhanced infiltration of immune cells into pancreatic islets during development of type 1 diabetes mellitus. In this study, we examined the regulatory effects and the mechanisms of action of celastrol against cytotoxicity and pro-inflammatory immune responses in the RINm5F rat pancreatic ${\beta}$-cell line stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha, and interferon-${\gamma}$. Celastrol significantly restored cytokine-induced cell death and significantly inhibited cytokine-induced nitric oxide production. In addition, the protective effect of celastrol was correlated with a reduction in pro-inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly suppressed cytokine-induced signaling cascades leading to nuclear factor kappa B (NF-${\kappa}B$) activation, including $I{\kappa}B$-kinase (IKK) activation, $I{\kappa}B$ degradation, p65 phosphorylation, and p65 DNA binding activity. These results suggest that celastrol may exert its cytoprotective activity by suppressing cytokine-induced expression of pro-inflammatory mediators by inhibiting activation of NF-${\kappa}B$ in RINm5F cells.

• 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.

• Journal of Nutrition and Health
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• 제51권4호
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• pp.323-329
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• 2018

만성 염증은 현대사회에서 다양한 질병을 유발하는 주요 원인으로 작용하기 때문에 항염증 활성을 가진 소재의 연구는 염증 관련 질병의 예방과 치료에 있어서 중요하다. 본 연구에서는 LPS에 의해 염증을 유도한 RAW 264.7 세포에서 제주왕지네 (Scolopendra subspinipes mutilans) 에탄올 추출물의 염증 조절 기전을 확인하여 항염증 소재로서의 가능성을 조사하였다. LPS에 의해 증가된 NO 생성과 iNOS 발현은 왕지네 추출물에 의해 감소되었고 pro-inflammatory cytokine으로 알려진 $IL-1{\beta}$, IL-6의 발현에서도 유사한 결과를 보였다. 왕지네 추출물은 LPS에 의해 유도된 $NF-{\kappa}B$의 핵으로의 전이와 $I{\kappa}B$의 분해를 동시에 억제하였고 $NF-{\kappa}B$ inhibitor의 처리는 NO 생성과 iNOS 발현을 더욱 억제하였다. 이상의 결과는 왕지네 추출물이 $NF-{\kappa}B$ 활성 조절을 통해 염증 반응의 지표로 사용되는 NO 생성 및 pro-inflammatory cytokine의 발현을 효과적으로 억제하여 항염 활성을 가진 소재로서의 가능성을 보여주는 것으로 염증에 의해 유발되는 다양한 질병을 효율적으로 제어하는 소재를 개발하는데 있어서 주요한 정보를 제공할 것으로 생각된다.

• 대한한방내과학회지
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• 제25권1호
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• pp.59-70
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• 2004

Objectives : Previous studies showed that treatment with Chungganhaeju-tang prevents hepatic inflammation and apoptosis in alcoholic liver disease. The purpose of our study is to determine if any relations exsists between the transcription factor $NF{\kappa}B$, an orchestrating expression of a large number of genes and inhibitory effects of Chungganhaeju-tang on ethanol induced apoptosis. Materials and Methods : To assess the role of $NF{\kappa}B$, we blocked NFkB activation by delivering to the kupffer cells $I{\kappa}B{\Delta}N$, a dominant negative $NF{\kappa}B$ inhibitor, and investigated if Chungganhaeju-tang still prevented apoptosis. Results : When $NF{\kappa}B$ activation was blocked, there was no inhibitory effect of Chungganhaeju-tang on ethanol induced apoptosis of kupffer cells. Conclusion : This result suggests that Chungganhaeju-tang protects the liver from ethanol induced apoptosis by activating the $NF{\kappa}B$ that plays a key role in porotecting mechanism and reducing inflammatory cytokine gene expression.

• IMMUNE NETWORK
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• 제14권1호
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• pp.14-20
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• 2014

CD28/T cell receptor ligation activates the NF-${\kappa}B$ signaling cascade during CD4 T cell activation. NF-${\kappa}B$ activation is required for cytokine gene expression and activated T cell survival and proliferation. Recently, many reports showed that NF-${\kappa}B$ activation is also involved in T helper (Th) cell differentiation including Th17 cell differentiation. In this review, we discuss the current literature on NF-${\kappa}B$ activation pathway and its effect on Th17 cell differentiation.