• BMB Reports
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• v.36 no.1
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• pp.66-77
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• 2003

Tea is one of the most popular beverages consumed in the world and has been demonstrated to have anti-cancer activity in animal models. Research findings suggest that the polyphenolic compounds, (-)-epigallocatechin-3-gallate, found primarily in green tea, and theaflavin-3,3'-digallate, a major component of black tea, are the two most effective anti-cancer factors found in tea. Several mechanisms to explain the chemopreventive effects of tea have been presented but others and we suggest that tea components target specific cell-signaling pathways responsible for regulating cellular proliferation or apoptosis. These pathways include signal transduction pathways leading to activator protein-1 (AP-1) and/or nuclear factor kappa B(NF-${\kappa}B$ ). AP-1 and NF-${\kappa}B$ are transcription factors that are known to be extremely important in tumor promoter-induced cell transformation and tumor promotion, and both are influenced differentially by the MAP kinase pathways. The purpose of this brief review is to present recent research data from other and our laboratory focusing on the tea-induced cellular signal transduction events associated with the MAP kinase, AP-1, and NF-${\kappa}B$ pathways.

• BMB Reports
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• v.35 no.6
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• pp.537-546
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• 2002

NF-${\kappa}B$/Rel transcription factor family participates in diverse biological processes including embryo development, hematopoiesis, immune regulation, as well as neuronal functions. In this review, the NF-${\kappa}B$/Rel signal transduction pathways and their important roles in the regulation of immune system will be discussed. NF-${\kappa}B$/Rel members execute distinct functions in multiple immune cell types via the regulation of target genes essential for cell proliferation, survival, effector functions, cell trafficking and communication, as well as the formation of lymphoid architecture. Consequently, proper activation of NF-${\kappa}B$/Rel during immune responses to allergens, auto-antigens, allo-antigens, and pathogenic infection is crucial for the integrity of host innate and adaptive immunity.

• BMB Reports
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• v.38 no.3
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• pp.281-289
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• 2005

Tumor necrosis factor (TNF) signaling is mediated via two distinct receptors, TNFR2 and TNFR1, which shows partially overlapping signaling mechanisms and biological roles. In the present study, TNFR2 and TNFR1 signal transduction mechanisms involved in activation of $NF{\kappa}B$ and CMV promoter-enhancer were compared with respect to their susceptibility towards inhibitors of intracellular signaling. For this, we used SW480 cells, where we have shown that TNF-signaling can occur independently through each of the two receptors. The TNFR1 response was inhibited by D609, bromophenacyl bromide (BPB), nordihydroguararetic acid (NDGA), and by sodium salicylate, while TNFR2-mediated activation of $NF{\kappa}B$ and CMV promoter-enhancer was resistant to these compounds. The signaling mechanisms known to be affected by these inhibitors include phospholipases as well as redox- and pH-sensitive intracellular components. Our results imply that TNFR2 signaling involved in $NF{\kappa}B$ activation proceeds independently of these inhibitor-sensitive signaling components, indicating distinct signaling pathways not shared with TNFR1.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1579-1583
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• 2013

Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin superfamily, its main function being to participate in recognition and adhesion between cells. ICAM-1 is considered closely related to occurrence, development, metastasis and invasion process of hepatocellular carcinoma (HCC). A variety of inflammatory cytokines and stimulus affect its expression through the nuclear factor-kappa B (NF-${\kappa}B$) signal transduction pathway. In the initial stage of inflammation, hepatocirrhosis and tumor development, ICAM-1 is expressed differently, and has varied effects on different cells to promote occurrence of malignancy and metastasis. ICAM-1 has diagnostic significance for AFP-negative or suspected HCC, and may be a prognositic significance. It is thus widely used in studies as a biomarker which reflects cancer cells metastasis as well as curative effect of drugs. Many new treatments of HCC may be based on the effects of ICAM-1 on different levels of function.

• BMB Reports
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• v.41 no.4
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• pp.328-333
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• 2008

A variety of anti-inflammatory agents have been shown to exert chemopreventive activity via targeting of transcription factors such as NF-${\kappa}B$ and AP-1. Lithospermum erythrorhizon (LE) has long been used in traditional oriental medicine. In this study, we demonstrated the inhibitory effects of LE extracts on lipopolysaccharide (LPS)-stimulated production of inflammatory cytokines. As an underlying mechanism of inhibition, LE extracts reduced LPS-induced transactivation of AP-1 as well as NF-${\kappa}B$ in mouse macrophage cells. Electrophoretic mobility shift assays indicated that LE extracts inhibited the DNA binding activities of AP-1 and NF-${\kappa}B$. In addition, phosphorylation of $I{\kappa}B-{\alpha}$ protein was suppressed by LE extracts. Moreover, LE extracts inhibited c-Jun N-terminal kinase and extracellular signal-regulated signaling pathways. Our results suggest that the anti-inflammatory activity of LE extracts may be mediated by the inhibition of signal transduction pathways that normally lead to the activation of AP-1and NF-${\kappa}B$. These inhibitory effects may be useful for chemoprevention of cancer or other chronic inflammatory diseases.

• BMB Reports
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• v.42 no.3
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• pp.148-153
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• 2009

Pyrrolidine dithiocarbamate (PDTC) is a stable anti-oxidant or pro-oxidant, depending on the situation, and it is widely used to inhibit the activation of NF-${\kappa}B$. We recently reported that PDTC activates the MIP-2 gene in a NF-${\kappa}B$-independent and c-Jun-dependent manner in macrophage cells. In this work, we found that PDTC activates signal transduction pathways in mouse ES cells. Among the three different mitogen-activated protein kinase (MAPK) pathways, including the extracellular-signal-regulated kinase (ERK), p38 MAP kinase, and stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) pathways, only the ERK pathway was significantly activated in mouse ES cells after stimulation with PDTC. Additionally, we observed a synergistic activation of ERK and induction of c-Fos after stimulation with PDTC in the presence of mouse embryonic fibroblast (MEF) conditioned medium. In contrast, another NF-${\kappa}B$ inhibitor, BMS-345541, did not activate the MAP kinase pathways or induce expression of c-Fos. These results suggest that changes in the presence of the NF-${\kappa}B$ inhibitor PDTC should be carefully considered when it used with mouse ES cells.

• Genomics & Informatics
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• v.17 no.1
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• pp.8.1-8.10
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• 2019

Alveolar type II cells constitute a small fraction of the total lung cell mass. However, they play an important role in many cellular processes including trans-differentiation into type I cells as well as repair of lung injury in response to toxic chemicals and respiratory pathogens. Transcription factors are the regulatory proteins dynamically modulating DNA structure and gene expression. Transcription factor profiling in microarray datasets revealed that several members of AP1, ATF, $NF-{\kappa}B$, and C/EBP families involved in diverse responses were expressed in mouse lung type II cells. A transcriptional factor signature consisting of Cebpa, Srebf1, Stat3, Klf5, and Elf3 was identified in lung type II cells, Sox9+ pluripotent lung stem cells as well as in mouse lung development. Identification of the transcription factor profile in mouse lung type II cells will serve as a useful resource and facilitate the integrated analysis of signal transduction pathways and specific gene targets in a variety of physiological conditions.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.56-56
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• 2021

Nypa fruticans Wurmb is a mangrove plant belonging to Araceae family. N. fruticans is typically found in Southeast Asia, and in some parts of Queensland, Australia. N. fruticans has phytochemicals, phenolics, and flavonoids. In this study, we investigated the anti-inflammatory effects of the ethyl acetate fraction of N. fruticans (ENF) on the production and expression of cytokines and inflammatory mediators through the major signal transduction pathways. ENF attenuated the level of cytokines in a dose-dependent manner and decreased the production of nitric oxide (NO). ENF decreased the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via alleviating transcription of nuclear factor-kappa B (NF-κB) by an inhibitor of nuclear factor-kappa B (IκB) degradation. Furthermore, mitogen-activated protein kinase (MAPK) signaling pathways (ERK1/2, JNK1/2, and p38) are known to be involved in the inflammatory response. Phosphorylations of ERK1/2, JNK1/2, and p38 were significantly decreased compared with the ENF-untreated control. Conclusively, ENF was related to alleviating various pro-inflammatory mediators through IκB/NF-κB and MAPK signaling pathways, including p65 translocation to the nucleus.

• IMMUNE NETWORK
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• v.3 no.4
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• pp.310-319
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• 2003

Inflammatory mediators has been recognized as an important role in the pathogenesis of rheumatoid arthritis (RA). IL-17 is increasingly recognized as an important regulator of immune and inflammatory responses, including induction of proinflammatory cytokines and osteoclastic bone resorption. Evidence of the expression and proinflammatory activity of IL-17 has been demonstrated in RA synovium and in animal models of RA. However, the signaling pathways that regulate IL-17 production remain unknown. In the present study, we investigated the role of the phosphatidylinositol 3 kinase (PI3K)-Akt pathway in the regulation of IL-17 production in RA. PBMC were separated from RA (n=24) patients, and stimulated with various agents (anti CD3, anti CD28, PHA, ConA, IL-15). IL-17 levels were determined by sandwich ELISA and RT-PCR. The production of IL-17 was significantly increased in cells treated with anti-CD3 antibody, PHA, IL-15 or MCP-1 (P<0.05). ConA also strongly induced IL-17 production (P<0.001), whereas TNF-alpha, IL-1beta, IL-18 or TGF-beta did not. IL-17 was detected in the PBMC of patients with osteoarthritis (OA) but their expression levels were much lower than those of RA PBMC. Anti-CD3 antibody activated the PI3K-Akt pathway and activation of the PI3K-Akt pathway resulted in a pronounced augmentation of nuclear factor kappaB ($NF-{\kappa}B$). IL-17 production by activated PBMC in RA is completely or partially blocked in the presence of $NF-{\kappa}B$ inhibitor PDTC and PI3K-Akt inhibitor, wortmannin and LY294002, respectively. Whereas the inhibition of AP-1 and extracellular signal-regulated kinase (ERK)1/2 did not affect IL-17 production. These results provide new insight into that PI3K/Akt and $NF-{\kappa}B$ dependent signal transduction pathway could be involved in the overproduction of key inflammatory cytokine, IL-17 in rheumatoid arthritis.

• Proceedings of the Korean Society of Toxicology Conference
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• 2005.05a
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• pp.85-90
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• 2005

Diesel exhaust Particles (DEPs) are known to induce allergic responses in airway epithelial cells, such as the production of various cytokines via nuclear factor-kappa B ($NF-{\kappa}B$). However. the intracellular signal transduction pathways underlying this phenomenon have not been fully examined. This study showed that DEP induced $NF-{\kappa}B$ activity via transforming growth factor-${\beta}$ activated kinase 1 (TAK1) and $NF-{\kappa}B$-inducing kinase (NIK) in L2 rat lung epithelial cells. DEP induced the $NF-{\kappa}B$ dependent reporter activity approximately two-to three-fold in L2 cells. However, this effect was abolished by the expression of the dominant negative forms of TAK1 or NIK. Furthermore, it was shown that DEP induced TAK1 phosphorylation in the L2 cells. These results suggest that TAK1 and NIK are important mediators of DEP-induced $NF-{\kappa}B$ activation.