• Title/Summary/Keyword: NF

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Knockdown of Bcl-3 Inhibits Cell Growth and Induces DNA Damage in HTLV-1-infected Cells)

  • Gao, Cai;Wang, Xia;Chen, Lin;Wang, Jin-Heng;Gao, Zhi-Tao;Wang, Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.405-408
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    • 2013
  • Oncoprotein Bcl-3 is perceived as an unusual member of $I{\kappa}B$ family since it can both stimulate and suppress NF-${\kappa}B$ activation. Aberrant Bcl-3 results in increased cell proliferation and survival, suggesting a contribution to malignant potential and elevated levels of Bcl-3 have been observed in many HTLV-1-infected T cell lines and ATL cells. To investigate the specific roles of Bcl-3 in HTLV-1-infected cells, we knocked down Bcl-3 expression using shRNA and then examined the consequences with regard to DNA damage and cell proliferation, as well as NF-${\kappa}B$ activation. The HTLV-1 encoded protein Tax promotes Bcl-3 expression and nuclear translocation. In HTLV-1-infected cells, Bcl-3 knockdown obviously induced DNA damage. Cell growth and NF-${\kappa}B$ activation were reduced in HTLV-1-infected or Tax positive cells when Bcl-3 expression was decreased. Together, our results revealed positive roles of Bcl-3 in DNA stabilization, growth and NF-${\kappa}B$ activation in HTLV-1-infected cells.

Cholera Toxin Disrupts Oral Tolerance via NF-κB-mediated Downregulation of Indoleamine 2,3-dioxygenase Expression

  • Kim, Kyoung-Jin;Im, Suhn-Young
    • Biomedical Science Letters
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    • v.23 no.3
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    • pp.175-184
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    • 2017
  • Cholera toxin (CT) is an ADP-ribosylating bacterial exotoxin that has been used as an adjuvant in animal studies of oral immunization. The mechanisms of mucosal immunogenicity and adjuvanticity of CT remain to be established. In this study, we investigated the role of indoleamine 2,3-dioxygenase (IDO), which participates in the induction of immune tolerance, in CT-mediated breakdown of oral tolerance. When IDO-deficient ($IDO^{-/-}$) mice and their littermates were given oral ovalbumin, significant changes in antibody responses, footpad swelling and $CD4^+$ T cell proliferation were not observed in $IDO^{-/-}$ mice. Feeding of CT decreased IDO expression in mesenteric lymph nodes (MLN) and Peyer's patch (PP). CT-induced downregulation of IDO expression was reversed by inhibitors of nuclear factor-kappa B (NF-${\kappa}B$), pyrrolidine dithiocarbamate and p50 small interfering RNA. IDO expression was downregulated by the NF-${\kappa}B$ inducers lipopolysaccharide and tumor necrosis factor-${\alpha}$. CT dampened IDO activity and mRNA expression in dendritic cells from MLN and PP. These data indicate that CT disrupts oral tolerance by activating NF-${\kappa}B$, which in turn downregulates IDO expression. This study betters the understanding of the molecular mechanism underlying CT-mediated abrogation of oral tolerance.

Analysis of Promoter Elements for Transcriptional Expression of Rat p53 Gene in Regenerating Liver

  • Lee, Min-Hyung;Song, Hai-Sun;Park, Sun-Hee;Choi, Jin-Hee;Yu, Sun-Hee;Park, Jong-Sang
    • BMB Reports
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    • v.32 no.1
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    • pp.45-50
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    • 1999
  • We previously found three transcription factor-binding motifs in the rat p53 promoter. They are two recognition motifs of NF1-like protein (NF1-like element 1: -296 ~ -312, NF1-like element 2: -195 ~ -219) and a bHLH protein binding element (-142 ~ -146). In this study, we investigated the DNA-protein complex formation of the three elements with nuclear extracts from both normal and regenerating liver to find the element involved in the induced transcription of p53. The level of each DNA-protein complex on NF1-like and bHLH motifs was not changed. Instead, a new element located at -264 ~ -284 was detected in the DNase I footprinting assay with regenerating nuclear extract. This element has partial homology to the AP1 consensus motif. However, the competition studies with diverse oligonucleotides suggest that the binding protein is not AP1. An in vitro transcription assay shows that this element is important for the transcriptional activation of the rat p53 promoter. Therefore, for the induced transcription of the rat p53 promoter, the-264 ~ -284 region is required in addition to two NF1-like and one bHLH motif.

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A Korean case of neurofibromatosis type 1 with an exonic splicing enhancer site mutation

  • Park, Sangwook;Sohn, Young Bae;Chung, In-Soon;Hong, Ji-Hee;Jung, Eun-Jung;Jeong, Seon-Yong;Jin, Hyun-Seok
    • Journal of Genetic Medicine
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    • v.11 no.1
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    • pp.40-42
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    • 2014
  • Neurofibromatosis type 1 (NF1) is an autosomal dominant disease characterized by neurological, cutaneous, and ophthalmological manifestations. A 33-year-old woman with typical symptoms of NF1 visited Ajou University Hospital. Screening of the whole-messenger RNA region of NF1 at the complementary DNA level by polymerase chain reaction-direct sequencing confirmed the presence of an NF1 mutation at the genomic level. The mutation analysis revealed an in-frame skipping of exon 46 (c.6757_6858del) caused by a point mutation (c. 6792C>A) in exon 46. In this report, we have described the first Korean case of a proband with NF1 that carries an allele with an exon 46 deletion caused by an exonic splicing enhancer site mutation, leading to the skipping of the whole of exon 46 (c.6757_6858del).

Cadmium but not Mercury Suppresses NF-$\kappa$B Activation and COX-2 Expression Induced by Toll-like Receptor 2 and 4 Agonists

  • Ahn, Sang-Il;Park, Seul-Ki;Lee, Mi-Young;Youn, Hyung-Sun
    • Molecular & Cellular Toxicology
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    • v.5 no.2
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    • pp.141-146
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    • 2009
  • Toll-like receptors (TLRs) induce innate immune responses by recognizing conserved microbial structural molecules. All TLR signaling pathways culminate in the activation of nuclear factor kappa-B (NF-$\kappa$B) leading to the induction of inflammatory gene products such as cyclooxygenase-2 (COX-2). Deregulated activation of TLRs can lead to the development of severe systemic inflammation. Divalent heavy metals, cadmium and mercury, have been used for thousands of years. While cadmium and mercury are clearly toxic to most mammalian organ systems, especially the immune system, their underlying toxic mechanism(s) remain unclear. Here, we report biochemical evidence that cadmium, but not mercury, inhibits NF-$\kappa$B activation and COX-2 expression induced by TLR2 or TLR4 agonists, while cadmium does not inhibit NF-$\kappa$B activation induced by the downstream signaling component of TLRs, MyD88. Thus, the target of cadmium to inhibit NF-$\kappa$B activation may be upstream of MyD88 including TLRs themselves, or events leading to TLR activation by agonists.

NF-${\kappa}B$ Inhibitory Activities of Phenolic and Lignan Components from the Stems of Acanthopanax divaricatus var. albeofructus

  • Sun, Ya Nan;Li, Wei;Song, Seok Bean;Yan, Xi Tao;Yang, Seo Young;Kim, Young Ho
    • Natural Product Sciences
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    • v.20 no.4
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    • pp.232-236
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    • 2014
  • Acanthopanax divaricatus var. albeofructus (ADA) is commonly ingested as a traditional medicine or as a component of a health drink in Korea. In this phytochemical study, nine phenolics (1 - 9) and three lignans (10 - 12) were isolated from the MeOH extract of the stems of ADA. Chemical structures were elucidated by comparing spectroscopic data with reported values. Nuclear factor kappa B ($NF-{\kappa}B$) inhibitory activity of the isolated compounds was evaluated using an $NF-{\kappa}B$ luciferase assay in HepG2 cells. Among them, compounds 1, 3 - 8, and 11 showed significant inhibitory effects on $TNF{\alpha}$-induced $NF-{\kappa}B$ transcriptional activity in a dosedependent manner, with $IC_{50}$ values ranging from 13.25 to $37.36{\mu}M$. Further studies on potential anti-inflammatory effects and the benefits of phenolic and lignan components from ADA are warranted.

Optical and Mechanical Characteristics of NF System and NF Gap Control (근접장 광학계의 광학적 및 기계적 특성 분석과 근접장 간격제어)

  • Oh, Hyeong-Ryeol;Lee, Jun-Hee;Gweon, Dae-Gab;Kim, Soo-Kyung
    • Proceedings of the Korean Society for Noise and Vibration Engineering Conference
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    • 2000.06a
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    • pp.1528-1532
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    • 2000
  • The conventional optics and near field optics are compared numerically in the view points of the spot size and propagation characteristics. The decaying characteristics of near field light require the optics to access the object within several tens of nanometers. Therefore the gap control is one of the main issues in the near field optics area. In this paper the gap control is done by using the shear force of the NF(Near Field) probe and the characteristics are examined. The probe is modeled as a 2'nd order mass-spring-damper system driven by a harmonic force. The primary cause of the decrease in vibration amplitude is due to the damping force - shear force - between the surface and the probe. Using the model, damping constant and resonance frequency of the probe is calculated as a function of probe-sample distance. Detecting the amplitude and phase shift of the NF probe attached to the high Q-factor piezoelectric tuning fork, we can control the position of the NF probe about 0 to 50nm above the sample. The feedback signal to regulate the probe-sample distance can be used independently for surface topography imaging. 3-D view of the shear force image of a testing sample with the period of $1{\mu}m$ will be shown.

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Curcumin Suppresses Activation of NF-κB and AP-1 Induced by Phorbol Ester in Cultured Human Promyelocytic Leukemia Cells

  • Han, Seong-Su;Keum, Young-Sam;Seo, Hyo-Joung;Surh, Young-Joon
    • BMB Reports
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    • v.35 no.3
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    • pp.337-342
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    • 2002
  • Many components that are derived from medicinal or dietary plants possess potential chemopreventive properties. Curcumin, a yellow coloring agent from turmeric (Curcuma longa Linn, Zingiberaceae), possesses strong antimutagenic and anticarcinogenic activities. In this study, we have found that curcumin inhibits the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced nuclear factor ${\kappa}B$ (NF-${\kappa}B$) activation by preventing the degradation of the inhibitory protein $I{\kappa}B{\alpha}$ and the subsequent translocation of the p65 subunit in cultured human promyelocytic leukemia (HL-60) cells. Alternatively, curcumin repressed the TPA-induced activation of NF-${\kappa}B$ through direct interruption of the binding of NF-${\kappa}B$ to its consensus DNA sequences. Likewise, the TPA-induced DNA binding of the activator protein-1 (AP-1) was inhibited by curcumin pretreatment.

Algorithm and Architecture of Hybrid Fuzzy Neural Networks (하이브리드 퍼지뉴럴네트워크의 알고리즘과 구조)

  • 박병준;오성권;김현기
    • 제어로봇시스템학회:학술대회논문집
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    • 2000.10a
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    • pp.372-372
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    • 2000
  • In this paper, we propose Neuro Fuzzy Polynomial Networks(NFPN) based on Polynomial Neural Network(PNN) and Neuro-Fuzzy(NF) for model identification of complex and nonlinear systems. The proposed NFPN is generated from the mutually combined structure of both NF and PNN. The one and the other are considered as the premise part and consequence part of NFPN structure respectively. As the premise part of NFPN, NF uses both the simplified fuzzy inference as fuzzy inference method and error back-propagation algorithm as learning rule. The parameters such as parameters of membership functions, learning rates and momentum coefficients are adjusted using genetic algorithms. As the consequence part of NFPN, PNN is based on Group Method of Data Handling(GMDH) method and its structure is similar to Neural Networks. But the structure of PNN is not fixed like in conventional Neural Networks and self-organizing networks that can be generated. NFPN is available effectively for multi-input variables and high-order polynomial according to the combination of NF with PNN. Accordingly it is possible to consider the nonlinearity characteristics of process and to get better output performance with superb predictive ability. In order to evaluate the performance of proposed models, we use the nonlinear function. The results show that the proposed FPNN can produce the model with higher accuracy and more robustness than any other method presented previously.

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Lonicera Japonica Inhibits Atopy Dermatitis in NC/Nga Mouse through Regulation of iNOS by NF-${\kappa}B$ Suppression (금은화의 NF-${\kappa}B$ 활성 억제를 통한 iNOS 조절이 NC/Nga 생쥐의 아토피 피부염에 미치는 영향)

  • Ahn, Sang-Hyun;Kim, Ho-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.2
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    • pp.278-283
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    • 2010
  • Inducible nitric oxide synthase (iNOS) are important inflammation enzyme and severe up-nitric oxide (NO) production by this enzyme has been intricate with pathogenesis of atopy dermatitis. The present study was designed in order to determine whether Lonicera japonica could inhibit atopy dermatitis through modulation of iNOS by NF-${\kappa}B$ suppression. We found that IKK mRNA and iNOS mRNA expression in RAW 264.7 macrophages stimulated with lipopolysaccharide dose-dependantly decreased by Lonicera japonica (0.4 - 1.0 mg/$m{\ell}$) and NO production decreased. The distribution of NF-${\kappa}B$ p65 and iNOS positive reacted cell in NC/Nga mice with atopy dermatitis were decreased by Lonicera japonica (45 mg/kg/day) and apoptosis were increased. These data likely indicate that Lonicera japonica may act as inflammatory regulator for atopy dermatitis through iNOS modulation by NF-${\kappa}B$B suppression and may be possible to develop useful agent for chemoprevention of NO intricate inflammatory diseases.