• Archives of Pharmacal Research
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• v.22 no.5
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• pp.454-458
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• 1999

TR8 is a recently identified member of the tumor necrosis factor (TNF) receptor superfamily. TR8 seems to play important roles in bone metabolism as stimulation of this receptor with its ligand, TL8 or osteoclast differentiation factor (ODF), induced the differentiation and activation of osteoclasts. Despite its important biological functions, the biochemcial events ensuing form TR8 activation have not been revealed in detail. Most of TNF receptor family proteins provoke the activation of the NF-$textsc{k}$B transcription factor. In the present study, we examined the signaling potential of TR8 to induce NF-B activation. When overexpressed in a human embryonic kidney cell line by transient transfection, TR8 caused a strong activation of NF-$textsc{k}$B, which was further increased upon stimulation with TL8. The TR8-induced NF-B activation was abrogated by the co-expression of the TRAF6 mutnat lacking the Ring and zinc finger domains and that of the kinase-inactive mutant NIK. Taken together, our study suggests that the presence of intact TRAF6 and the kiase activity of NIK may be essential for TR8 to induce NF-$textsc{k}$B activation.

• Archives of Pharmacal Research
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• v.24 no.4
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• pp.307-311
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• 2001

The activation of NF-$\kappa$B induced by kojic Acid, an inhibitor of tyrosinase for biosynthesis of melanin in melanocytes, was investigated in human transfectant HaCaT and SCC-13 cells. These two keratinocyte cell lines transfected with pNF-$\kappa$B-SEAP-NPT plasmid were used to determine the activation of NF-$\kappa$B. Transfectant cells release the secretory alkaline phosphatase (SEAP) as a transcription reporter in response to the NF-$\kappa$B activity and contain the neomycin phosphotransferase (NPT) gene for the dominant selective marker of geneticin resistance. NF-$\kappa$B activation was measured in the SEAP reporter gene assay using a fluorescence detection method. Kojic Acid showed the inhibition of cellular NF-$\kappa$B activity in both human keratinocyte transfectants. It could also downregulate the ultraviolet ray (UVR)-induced activation of NF-$\kappa$B expression in transfectant HaCaT cells. Moreover, the inhibitory activity of kojic Acid in transfectant HaCaT cells was found to be more potent than known antioxidants, e.g., vitamin C and N~acetyl-L-cysteine. These results indicate that kojic Acid is a potential inhibitor of NF-$\kappa$B activation in human keratinocytes, and suggest the hypothesis that NF-$\kappa$B activation may be involved in kojic Acid induced anti-melanogenic effect.

• Animal cells and systems
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• v.1 no.1
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• pp.63-69
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• 1997

We have previously reported that NF-kB is involved in the regulation of nitric oxide synthase gene expression during differentiation of chick embryonic myoblasts. However, how NF-kB is timely activated during myogenesis remains elusive. One of the most prominent events in myogenesis is myoblast membrane fusion, which is accompanied with massive cytoskeletal reorganization. Here we show that the activity of NF-kB markedly increases in L6 rat myogenic cells that have just initiated morphological changes by treating nocodazole, a microtubule-disrupting agent. Furthermore, the induction of NF-kB activation was closely correlated with the myoblast fusion. In addition, a variety of agents that disrupt microtubules stimulated the myoblast fusion as well as the induction of NF-kB activation. In contrast, taxol, a microtubule-stabilizing agent, suppressed the induction of NF-kB activation and inhibited spontaneous differentiation of L6 cells as well. In addition, we found that the NF-KB in the cells consists of p50/p65 heterodimers. These results support the idea that reorganization of microtubule at early stages of differentiation plays a role as a signal for NF-KB activation during myogenesis.

• IMMUNE NETWORK
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• v.14 no.1
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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.

• Journal of Microbiology
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• v.37 no.4
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• pp.256-262
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• 1999

Latent membrane protein 1 (LMP1) of the Epstein-Barr virus (EBV) is an integral membrane protein with six transmembrane domains, which is essential for EBV-induced B cell transformation. LMP1 functions as a constitutively active tumor necrosis factor receptor (TNFR) like membrane receptor, whose signaling requires recruitment of TNFR-associated factors (TRAFs) and leads to NF-${\kappa}B$ activation. NF-${\kappa}B$ activation by LMP1 is critical for B cell transformation and has been linked to many phenotypic changes associated with EBV-induced B cell transformation. Deletion analysis has identified two NF-${\kappa}B$ activation regions in the carboxy terminal cytoplasmic domains of LMP1, termed CTAR1 (residues 194-232) and CTAR2 (351-386). The membrane proximal C-terminal domain was precisely mapped to a PXQXT motif (residues 204-208) involved in TRAF binding as well as NF-${\kappa}B$ activation. In this study, we dissected the CTAR2 region, which is the major NF-${\kappa}B$ signaling effector of LMP1, to determine a minimal functional sequence. A series of LMP1 mutant constructs systematically deleted for the CTAR2 region were prepared, and NF-${\kappa}B$ activation activity of these mutants were assessed by transiently expressing them in 293 cells and Jurkat T cells. The NF-${\kappa}B$ activation domain of CTAR2 appears to reside in a stretch of 6 amino acids (residues 379-384) at the end of the carboxy terminus.

• Journal of Microbiology and Biotechnology
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• v.19 no.6
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• pp.556-559
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• 2009

Compounds extracted from Platycodon grandiflorum were evaluated for an activation effect on nuclear factor-kappa B (NF-${\kappa}B$). In its active state, NF-${\kappa}B$ turns on the expression of genes related to cell proliferation or death. NF-${\kappa}B$ activators promote growth of neuron cells and can be used to control neurodegenerative diseases. The biological activity of P. grandiflorum extracts toward NF-${\kappa}B$ had not yet been studied. Although the biological activity of several compounds extracted from P. grandiflorum was evaluated, only three exhibited any significant activation effect on NF-${\kappa}B$.

• Korean Journal of Pharmacognosy
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• v.34 no.2 s.133
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• pp.156-160
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• 2003

$NF-{\kappa}B$ (nuclear factor-kappa B) plays a particularly central role in epidermal biology. It has been established that ultraviolet radiation (UVR) is one of the mechanisms to induce the activation of $NF-{\kappa}B$ in human skin. We previously demonstrated that melanogenic inhibitors may act through the inhibition of $NF-{\kappa}B$ activation in keratinocytes. In order to find another type of melanogenic inhibitors of $NF-{\kappa}B$ activation, various kinds of the extracts from crude drugs $(30\;{\mu}g/ml)$ were preincubated with transfectant HaCaT cells for 3 hrs and then UVR $(60\;mj/cm^2)$ was irradiated. UVR-exposed cells were incubated for another 6 hrs to measure the $NF-{\kappa}B$ activity. $NF-{\kappa}B$ activation was measured with the secreatory alkaline phosphates (SEAP) reporter gene assay using a fluorescence detection method. Among natural products, Lycium chinense, Acanthopanax senticosus, Angelica koreana, Kalopanax pictus and Asparagus cochinchinensis were the most potent inhibitors of $NF-{\kappa}B$ activation by UVR. These observations suggest that some crude drugs might act partially through the modulation of the synthesis of melanotrophic factors to decrease melanogenesis in keratinocytes.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.1
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• pp.11-18
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• 1999

Nuclear factor $_{\kappa}B\;(NF-_{\kappa}B)$ activation is modulated by various protein kinases. Activation of $NF-_{\kappa}B$ is known to be important in the regulation of cell viability. The present study investigated the effect of inhibitors of protein tyrosine kinase (PTK), protein kinase C (PKC) and protein kinase A (PKA) on $NF-_{\kappa}B$ activity and the viability of bovine cerebral endothelial cells (BCECs). In serum-deprivation-induced BCEC death, low doses of $TNF{\alpha}$ showed a protective effect. $TNF{\alpha}$ induced $NF-_{\kappa}B$ activation within 4 h in serum-deprivation. PTK inhibitors (herbimycin A and genistein) and PKC inhibitor (calphostin C) prevented $NF-_{\kappa}B$ activation stimulated by $TNF{\alpha}.$ Likewise, these inhibitors prevented the protective effect of $TNF{\alpha}.$ In contrast to $TNF{\alpha}-stimulated\;NF-_{\kappa}B$ activity, basal $NF-_{\kappa}B$ activity of BCECs in media containing serum was suppressed only by calphostin C, but not by herbimycin A. As well BCEC death was also induced only by calphostin C in serum-condition. H 89, a PKA inhibitor, did not affect the basal and $TNF{\alpha}-stimulated\;NF-_{\kappa}B$ activities and the protective effect of $TNF{\alpha}$ on cell death. These data suggest that modulation of $NF-_{\kappa}B$ activation could be a possible mechanism for regulating cell viability by protein kinases in BCECs.

• Toxicological Research
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• v.17
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• pp.89-96
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• 2001

Recently, considerable attention has been focused on the role of cyclooxygenase-2 (COX-2) in the carcinogenesis as well as in inflammation. Improperly overexpressed COX-2 has been observed in many types of human cancers and transformed cells in culture. Thus, it is conceivable that targeted inhibition of abnormally or improperly up-regulated COX-2 provides one of the most effective and promising strategies for cancer prevention. A ubiquitous eukaryotic transcription factor, NF-kB is considered to be involved in regulation of COX-2 expression. Furthermore, extracellular-regulated protein kinase and p38 mitogen-activated protein (MAP) kinase appear to be key elements of the intracellular signaling cascades involved in NF-kB activation in response to a wide array of external stimuli. Certain chemopreventive phytochemicals suppress activation of NF-kB by blocking one or more of the MAP kinases, which may contribute to their inhibitory effects on COX-2 induction. One of the plausible mechanisms by which chemopreventive phytochemicals inhibit NF-kB activation involves suppression of degradation of the inhibitory unit I kB, which hampers subsequent translocation of p65, the functionally active subunit of NF-kB.

• Korean Journal of Pharmacognosy
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• v.35 no.3 s.138
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• pp.244-249
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• 2004

The effects of hesperetin and naringenin on $NF-{\kappa}B$ activation were investigated in normal rat kidney cells transformed by temperature sensitive Rous Sarcoma Virus (tsNRK). The flavonoids, naringenin and hesperetin, significantly reduced v-Src-induced $NF-{\kappa}B$ activation as well as phosphorylation of Akt and GSK-3 in tsNRK cells, whereas these compounds did not effect on platelet-derived growth factor (PDGF)-induced $NF-{\kappa}B$ activation in $NIH3T3{\gamma}l$ cells. In addition, the DNA binding activity of SP-I was also reduced but that of AP-1 was not affected by the compounds. Our study suggests that Src-induced $NF-{\kappa}B$ activation could occur via Akt-GSK-3 pathway without $IkB{\alpha}$ degradation and that naringenin and hesperetin could be used in the treatment of cancer through the inhibition of $NF-{\kappa}B$ activation.