• Food Science and Biotechnology
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• 제17권6호
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• pp.1294-1298
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• 2008

Toll-like receptors (TLRs) induce innate immune responses recognizing conserved microbial structural molecules. All TLR signaling pathways culminate in the activation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$). The activation of NF-${\kappa}B$ leads to the induction of inflammatory gene products such as cyclooxygenase-2 (COX-2). Guggul has been used for centuries to treat a variety of diseases. Guggulstreone, one of the active ingredients in guggul, has been used to treat many chronic diseases. However, the mechanism as to how guggulsterone mediate the health effects is largely unknown. Here, we report biochemical evidence that guggulsterone inhibits the NF-${\kappa}B$ activation and COX-2 expression induced by TLR2, TLR3, and TLR4 agonists. Guggulsterone also inhibits the NF-${\kappa}B$ activation induced by downstream signaling components of TLRs, myeloid differential factor 88 (MyD88), $I{\kappa}B$ kinase ${\beta}$ ($IKK{\beta}$), and p65. These results imply that guggulsterone can modulate the immune responses regulated by TLR signaling pathways.

• IMMUNE NETWORK
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• 제3권1호
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• pp.38-46
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• 2003

Background: Platelet-activating factor (PAF) induces nuclear factor $(NF)-{\kappa}B$ activation and angiogenesis and increases tumor growth and pulmonary tumor metastasis in vivo. The role of $NF-{\kappa}B$ activation in PAF-induced angiogenesis in a mouse model of Matrigel implantation, and in PAF-mediated pulmonary tumor metastasis were investigated. Methods: Angiogenesis using Matrigel and experimental pulmonary tumor metastasis were tested in a mouse model. Electrophoretic mobility shift assay was done for the assessment of $NF-{\kappa}B$ translocation to the nucleus. Expression of angiogenic factors, such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\alpha}$, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were tested by RT-PCR and ELISA. Results: PAF induced a dose- and time-dependent angiogenic response. PAF-induced angiogenesis was significantly blocked by PAF antagonist, CV6209, and inhibitors of $NF-{\kappa}B$ expression or action, including antisense oligonucleotides to p65 subunit of $NF-{\kappa}B$ (p65 AS) and antioxidants such as ${\alpha}$-tocopherol and N-acetyl-L-cysteine. In vitro, PAF activated the transcription factor, $NF-{\kappa}B$ and induced mRNA expression of $TNF-{\alpha}$, $IL-1{\alpha}$, bFGF, VEGF, and its receptor, KDR. The PAF-induced expression of the above mentioned factors was inhibited by p65 AS or antioxidants. Also, protein synthesis of VEGF was increased by PAF and inhibited by p65 AS or antioxidants. The angiogenic effect of PAF was blocked when anti-VEGF antibodies was treated or antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF was co-administrated, but not by antibodies against $TNF-{\alpha}$, $IL-1{\alpha}$, and bFGF each alone. PAF-augmented pulmonary tumor metastasis was inhibited by p65 AS or antioxidants. Conclusion: These data indicate that PAF increases angiogenesis and pulmonary tumor metastasis through $NF-{\kappa}B$ activation and expression of $NF-{\kappa}B$-dependent angiogenic factors.

• Journal of Acupuncture Research
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• 제36권2호
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• pp.80-87
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• 2019

Background: This study investigated the anti-inflammatory effects of bee venom (BV) through the inhibition of nuclear factor kappa beta ($NF-{\kappa}B$) expression in macrophages and keratinocytes. Methods: Cell viability assays were performed to investigate the cytotoxicity of BV in activated macrophages [lipopolysaccharide (LPS)] and keratinocytes [interferon-gamma/tumor necrosis factor-alpha ($IFN-{\gamma}/TNF-{\alpha}$)]. A luciferase assay was performed to investigate the cellular expression of $NF-{\kappa}B$ in relation to BV dose. The expression of $NF-{\kappa}B$ inhibitors ($p-I{\kappa}B{\alpha}$, $I{\kappa}B{\alpha}$, and p50 and p65) were determined by Western Blot analysis, and the electromobility shift assay. A nitrite quantification assay was performed to investigate the effect of BV, and $NF-{\kappa}B$ inhibitor on nitric oxide (NO) production in macrophages. In addition, Western Blot analysis was performed to investigate the effect of BV on the expression of mitogen-activated protein kinases (MAPK) in activated macrophages and keratinocytes. Results: BV was not cytotoxic to activated macrophages and keratinocytes. Transcriptional activity of $NF-{\kappa}B$, and p50, p65, and $p-I{\kappa}B{\alpha}$ expression was reduced by treatment with BV in activated macrophages and keratinocytes. Treatment with BV and an $NF-{\kappa}B$ inhibitor, reduced the production of NO by activated macrophages, and also reduced $NF-{\kappa}B$ transcriptional activity in activated keratinocytes (compared with either BV, or $NF-{\kappa}B$ inhibitor treatment). Furthermore, BV decreased p38, p-p38, JNK, and p-JNK expression in LPS-activated macrophages and $IFN-{\gamma}/TNF-{\alpha}$-activated keratinocytes. Conclusion: BV blocked the signaling pathway of $NF-{\kappa}B$, which plays an important role in the inflammatory response in macrophages and keratinocytes. These findings provided the possibility of BV in the treatment of atopic dermatitis.

• 한국임상수의학회지
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• 제28권2호
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• pp.190-195
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• 2011

본 연구에서 돼지 PBMC에 t10c12-CLA 처리는 TNF-${\alpha}$생산을 증가시켰으나, LPS 자극 PBMC에서는 TNF-${\alpha}$생산을 감소시켰다. t10c12-CLA 처리는 PBMC의 inhibitory ${\kappa}B$ ($I{\kappa}B$)-${\alpha}$ 단백질 분해를 증가시키고 NF-${\kappa}B$ p65 활성 수준을 증가시켰다. 그러나 LPS 자극 PBMC에서는 상반되는 효과가 관찰되었다. 특히, LPS 비자극 PBMC에서 t10c12-CLA는 NF-${\kappa}B$ 저해제인 caffeic acid phenethyl ester (CAPE)를 처리한 경우 NF-${\kappa}B$ p65 활성 수준을 증가시켰으나 반대로 LPS로 자극한 CAPE 처리 PBMC에서는 NF-${\kappa}B$ p65 활성 수준을 억제시켰다. 이상의 결과는 t10c12-CLA가 돼지 PBMC에 있어 LPS 자극 유무에 따라 다른 효과를 가질 수 있으며, 이는 NF-${\kappa}B$ p65 활성도의 변화와 관련성이 있음을 보여주고 있다.

• Molecules and Cells
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• 제25권2호
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• pp.253-257
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• 2008

Acrolein is a highly electrophilic ${\alpha},{\beta}$-unsaturated aldehyde present in a number of environmental sources, especially cigarette smoke. It reacts strongly with the thiol groups of cysteine residues by Michael addition and has been reported to inhibit nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) activation by lipopolysaccharide (LPS). The mechanism by which it inhibits $NF-{\kappa}B$ is not clear. Toll-like receptors (TLRs) play a key role in sensing microbial components and inducing innate immune responses, and LPS-induced dimerization of TLR4 is required for activation of downstream signaling pathways. Thus, dimerization of TLR4 may be one of the first events involved in activating TLR4-mediated signaling pathways. Stimulation of TLR4 by LPS activates both myeloid differential factor 88 (MyD88)- and TIR domain-containing adapter inducing $IFN{\beta}$ (TRIF)-dependent signaling pathways leading to activation of $NF-{\kappa}B$ and IFN-regulatory factor 3 (IRF3). Acrolein inhibited $NF-{\kappa}B$ and IRF3 activation by LPS, but it did not inhibit $NF-{\kappa}B$ or IRF3 activation by MyD88, inhibitor ${\kappa}B$ kinase $(IKK){\beta}$, TRIF, or TNF-receptor-associated factor family member-associated $NF-{\kappa}B$ activator (TANK)-binding kinase 1 (TBK1). Acrolein inhibited LPS-induced dimerization of TLR4, which resulted in the down-regulation of $NF-{\kappa}B$ and IRF3 activation. These results suggest that activation of TLRs and subsequent immune/inflammatory responses induced by endogenous molecules or chronic infection can be modulated by certain chemicals with a structural motif that enables Michael addition.

• 한국임상수의학회지
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• 제29권5호
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• pp.361-367
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• 2012

고혈당으로 야기된 염증은 당뇨병에서 합병증을 일으키는 주된 요인이다. 최근 연구에 따르면 면역세포에서 TNF-${\alpha}$ 같은 염증성 cytokine의 과도한 생성은 인슐린 저항성을 야기시킨다고 한다. Conjugated linoleic acid (CLA)는 TNF-${\alpha}$ 생산에 관여하여 면역반응을 조절하는 것으로 알려져 있다. 본 연구는 고농도의 당으로 처리한 RAW 264.7 세포에서 TNF-${\alpha}$ 생산, NF-${\kappa}B$의 활성과 $I{\kappa}B-{\alpha}$ 분해에 대한 CLA 효과를 검토하였다. 고농도의 당에 노출된 RAW세포는 저농도의 당에 노출된 RAW 세포보다 NF-${\kappa}B$의 활성과 $I{\kappa}B-{\alpha}$ 분해가 증가되었으며 RAW 세포의 배양 상층액 중에 TNF-${\alpha}$ 생산을 증가시켰다. CLA와 고농도 또는 저농도의 당을 같이 처리한 군은 당만 단일 처리한 군보다 TNF-${\alpha}$ 생산, NF-${\kappa}B$의 활성 및 $I{\kappa}B-{\alpha}$ 분해가 증가되었다. 그리고 고농도의 당과 CLA를 처리한 군에서 저농도의 당과 CLA 처리군에 비해 NF-${\kappa}B$의 활성과 $I{\kappa}B-{\alpha}$ 분해가 증가되었으며 이와 더불어 TNF-${\alpha}$의 양이 증가되었다. 이상의 결과로부터, CLA는 고농도의 당에 노출된 RAW 세포에서 NF-${\kappa}B$의 활성을 높이고 TNF-${\alpha}$ 생산을 증가시키며 이는 고혈당으로 유발되는 염증반응을 촉진하는 인자로 작용할 수 있음을 시사하였다.

• 대한화장품학회지
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• 제32권3호
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• pp.135-140
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• 2006

Nucler factor-kappa B (NF-kappaB) 프로모터는 염증성 질환을 유도하는 호염증성 시토카인의 발현에 중요한 역할을 수행하는 전사인자 중의 하나이다. 본 실험에서는 200 여종의 식물추출물들로부터 항염효능이 있는 추출물을 선발하기 위해 NF-kappaB 리포터 실험을 수행하였다. NF-kappaB 리포터 실험결과, 12종의 식물추출물, 즉 개나리, 고추잎, 박하, 뱀딸기, 뽕나무, 삼백초, 솔잎, 양애줄기, 약쑥, 어성초, 왕벚꽃가지, 조릿대 등이 lipopolysaccharide (LPS)에 의해 유도된 NF-kappaB 프로모터 활성을 농도의존적으로 억제하는 것을 확인하였다. 이들 12종의 식물추출물이 호염증성 시토카인 발현에도 동일한 효과를 나타내는지 알아보기 위해 tumor necrosis factor-alpha (TNF alpha)와 인터루킨-8에 대한 ELISA실험을 실시하였다. ELISA실험 결과, NF-kappaB 리포터 실험결과와 동일하게, TNF-alpha와 인터루킨-8 생산이 12종 식물추출물 모두에서 감소됨을 관찰하였다. 이러한 실험결과는, 12종의 식물 추출물에서 보여지는 호염증성 시토카인 억제효과가 NF-kappaB 프로모터 활성억제를 통해 이루어지고 있음을 시사한다. 또한, 이들 12종 식물은 diphenyl-p-picrylhydrazyl (DPPH) assay를 통해 살펴본 결과 높은 항산화 활성도 있음을 확인하였다. 이상의 결과로부터, 12종의 식물 추출물은 염증성 피부질환 전용 화장품 제형에서 항염 및 자극완화 소재로 응용될 수 있음을 확인하였다.

• Biomolecules & Therapeutics
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• 제22권6호
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• pp.525-531
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• 2014

In the present study, we investigated whether apigenin significantly affects tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced production and gene expression of MUC5AC mucin in airway epithelial cells. Confluent NCI-H292 cells were pretreated with apigenin for 30 min and then stimulated with TNF-${\alpha}$ for 24 h or the indicated periods. The MUC5AC mucin gene expression and mucin protein production were measured by reverse transcription - polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Apigenin significantly inhibited MUC5AC mucin production and down-regulated MUC5AC gene expression induced by TNF-${\alpha}$ in NCI-H292 cells. To elucidate the action mechanism of apigenin, effect of apigenin on TNF-${\alpha}$-induced nuclear factor kappa B (NF-${\kappa}B$) signaling pathway was also investigated by western blot analysis. Apigenin inhibited NF-${\kappa}B$ activation induced by TNF-${\alpha}$. Inhibition of inhibitory kappa B kinase (IKK) by apigenin led to the suppression of inhibitory kappa B alpha ($I{\kappa}B{\alpha}$) phosphorylation and degradation, p65 nuclear translocation. This, in turn, led to the down-regulation of MUC5AC protein production in NCI-H292 cells. Apigenin also has an influence on upstream signaling of IKK because it inhibited the expression of adaptor protein, receptor interacting protein 1 (RIP1). These results suggest that apigenin can regulate the production and gene expression of mucin through regulating NF-${\kappa}B$ signaling pathway in airway epithelial cells.

• Journal of Korean Biological Nursing Science
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• 제14권2호
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• pp.129-138
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• 2012

Purpose: Cachexia is a complex metabolic syndrome associated with wasting of skeletal muscle which contributes to nearly one-third of all cancer deaths. Cachexia lowers the frequency of response to chemotherapy and radiation and ultimately can impact survival as well as quality of life during treatment. NF-kappa B is one of the most important molecular mediators of cachexia. In this study, therefore, possible candidates for inhibitors of NF-kappa B were searched. Methods: Amino acids that regulate cellular redox potential by adjusting the level of NAD/NADH ratio, such as aspartate, pyruvate, and isocitrate were selected. Results: Pyruvate effectively inhibited luciferase activity in TNF-stimulated 293T cells transfect with an NF-kB dependent luciferase reporter vector. Pyruvate also showed protective effect on muscle atrophy of differentiated C2C12 myocyte induced by TNF/IFN. Conclusion: We might be able to develop the nutritional management strategy for cancer cachexia patients with pyruvate supplementation.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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• pp.120.1-120.1
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• 2003

Nuclear factor-${\kappa}{B}$ (NF-${\kappa}{B}$) belongs to a group of homodimers and heterodimers of Rel/NF-${\kappa}{B}$ proteins that bind to DNA target sites, where they directly regulate gene transcription. The activation of NF-${\kappa}{B}$ has been shown to mediate inflammation and suppress apoptosis. Activated NF-${\kappa}{B}$ has been found n various inflammatory diseases such as rheumatoid arthritis, Atherosclerosis, asthma, nflammatory bowel disease, and Helicobacter pylori-associated gastritis and associated with cancer, cachexia, diabetes, euthyroid sick syndrome, and AIDS. (omitted)