• Journal of Microbiology and Biotechnology
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• 제24권1호
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• pp.127-131
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• 2014

While searching for lactic acid bacteria that can restore aging-impaired immune responses, we isolated the Toll-like receptor (TLR) 2/NF-${\kappa}B$-activating strain Lactobacillus plantarum HY7712 from kimchi and investigated its immunomodulating effect in whole-body ${\gamma}$-irradiated mice. Exposure to HY7712 strongly activated NF-${\kappa}B$ signaling in RAW264.7 cells, but inhibited lipopolysaccharide-stimulated NF-${\kappa}B$ activation. Moreover, HY7712 protected against the downregulation of interferon (IFN)-${\gamma}$ and upregulation of interleukin (IL)-13 caused by ${\gamma}$-irradiation in mice. In mice, ${\gamma}$-irradiation impaired NK-cell activity against YAC-1 tumor cells, but following HY7712 exposure, the activity of NK cells was restored to 91.5% of the level measured in control mice (p < 0.05). These findings suggest that HY7712 activates the TLR2/NF-${\kappa}B$ signaling pathway and protects against the impairment of NK-cell activity caused by ${\gamma}$-irradiation or aging.

• BMB Reports
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• 제48권10호
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• pp.571-576
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• 2015

SB743921 is a potent inhibitor of the spindle protein kinesin and is being investigated in ongoing clinical trials for the treatment of myeloma. However, little is known about the molecular events underlying the induction of cell death in multiple myeloma (MM) by SB743921, alone or in combination treatment. Here, we report that SB743921 induces mitochondria-mediated cell death via inhibition of the $NF-{\kappa}B$ signaling pathway, but does not cause cell cycle arrest in KMS20 MM cells. SB743921-mediated inhibition of the $NF-{\kappa}B$ pathway results in reduced expression of SOD2 and Mcl-1, leading to mitochondrial dysfunction. We also found that combination treatment with SB743921 and bortezomib induces death in bortezomib-resistant KMS20 cells. Altogether, these data suggest that treatment with SB743921 alone or in combination with bortezomib offers excellent translational potential and promises to be a novel MM therapy.

• BMB Reports
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• 제53권4호
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• pp.218-222
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• 2020

Excessive and hyperactive osteoclast activity causes bone diseases such as osteoporosis and periodontitis. Thus, the regulation of osteoclast differentiation has clinical implications. We recently reported that dehydrocostus lactone (DL) inhibits osteoclast differentiation by regulating a nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), but the underlying mechanism remains to be elucidated. Here we demonstrated that DL inhibits NFATc1 by regulating nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and nuclear factor-erythroid 2-related factor 2 (Nrf2). DL attenuated IκBα phosphorylation and p65 nuclear translocation as well as decreased the expression of NF-κB target genes and c-Fos. It also inhibited c-Jun N-terminal kinase (JNK) but not p38 or extracellular signal-regulated kinase. The reporter assay revealed that DL inhibits NF-κB and AP-1 activation. In addition, DL reduced reactive oxygen species either by scavenging them or by activating Nrf2. The DL inhibition of NFATc1 expression and osteoclast differentiation was less effective in Nrf2-deficient cells. Collectively, these results suggest that DL regulates NFATc1 by inhibiting NF-κB and AP-1 via down-regulation of IκB kinase and JNK as well as by activating Nrf2, and thereby attenuates osteoclast differentiation.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4277-4283
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• 2015

Anthocyanin, a phenolic compound, has been reported to have an anti-inflammatory effect against lipopolysaccharide (LPS) induced changes in immune cells. However, little is known about the molecular mechanisms underlying its anti-inflammatory effects. Few research studies have concerned the anti-inflammation properties of colored rice extract as a functional material. Therefore, the purpose of this study was to examine anti-inflammatory effects of the polar fraction of black rice whole grain extracts (BR-WG-P) that features a high anthocyanin content. Our results showed that BR-WG-P significantly inhibited LPS-induced pro-inflammatory mediators, including production of NO and expression of iNOS and COX-2. In addition, secretion of pro-inflammatory cytokines including TNF-${\alpha}$ and IL-6 was also significantly inhibited. Moreover, BR-WG-P and anthocyanin inhibited NF-kB and AP-1 translocation into the nucleus. BR-WG-P also decreased the phosphorylation of ERK, p38 and JNK in a dose dependent manner. These results suggested that BR-WG-P might suppress LPS-induced inflammation via the inhibition of the MAPK signaling pathway leading to decrease of NF-kB and AP-1 translocation. All of these results indicate that BR-WG-P exhibits therapeutic potential associated with the anthocyanin content in the extract for treating inflammatory diseases associated with cancer.

• BMB Reports
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• 제41권11호
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• pp.784-789
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• 2008

Mac-2BP is a ligand of the galectin family that has been suggested to affect tumor proliferation and metastasis formation. We assessed Mac-2BP expression at the transcriptional and translational levels to evaluate nerve growth factor (NGF)-induced Mac-2BP expression. A time kinetic analysis using reverse transcription-polymerase chain reaction showed that NGF-induced Mac-2BP transcript levels were 4-5 times higher than in controls. Mac-2BP enzyme-linked immunosorbent assay and immuno-fluorescence staining showed a 2-3-fold increase in intracellular and secreted Mac-2BP as a result of NGF stimulation. This increase was regulated by Akt activation and NF-${\kappa}B$ binding. p65 and p50-NF-${\kappa}B$ are major transcriptional factors in the Mac-2BP promoter region, and were shown to be regulated in accordance with the Akt activation states. Collectively, these results suggest that NGF induces Mac-2BP expression via the PI3K/Akt/NF-${\kappa}B$ pathway.

• 대한한의학방제학회지
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• 제24권4호
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• pp.243-257
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• 2016

Objectives : Illicium verum Hook. f. has been known to possess antimicrobial, antioxidant, antifungal, anti-inflammatory, insecticidal, analgesic, sedative, convulsive activities, it has been rarely conducted to evaluate the immuno-biological activity. The present study was examined to evaluate the anti-inflammatory effects of the Illicium verum Hook. f. water extracts (IVE) in vivo and in vitro. Methods : Cell viability was measured by MTT assay. The relative levels of NO were measured with Griess reagent. iNOS, COX-2, $NF-{\kappa}B$ and target proteins were detected by immunoblot analysis, and levels of cytokines were analyzed by ELISA kit. Anti-edema effect was determined in the carrageenan (CA)-induced paw edema model in rats. Results : All dosages of IVE used in MTT assay had no significant cytotoxicity. The increases of NO production and iNOS expression were detected in LPS-treated cells compared with control. However, these increases were attenuated by treatment with IVE. Also, IVE reduced the elevated production of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 by LPS. IVE inhibited the $p-I{\kappa}B$ and translocation of $NF-{\kappa}B$ to nuclear. Furthermore, IVE significantly inhibited the increases of hind paw swelling, skin thicknesses and inflammatory cell infiltrations induced by CA injection. Therefore, IVE will be favorably inhibited the acute edematous inflammations. Conclusion : These results provide evidences that anti-inflammatory effect of IVE is partly due to the reduction of some inflammatory mediators by suppression of $NF-{\kappa}B$ pathway.

• Natural Product Sciences
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• 제16권4호
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• pp.265-270
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• 2010

The methanol extract of Zanthoxylum rhetsa (MZRR) were evaluated for its ability to suppress the formation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophages. MZRR presented an inhibition of LPS-induced production of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) in RAW 264.7 macrophages. Western blotting and RT-PCR analyses demonstrated that MZRR significantly inhibited the protein and mRNA expressions of iNOS and COX-2 in LPS-activated macrophages in a dose-dependent manner. LPS-induced COX-2, iNOS, and nuclear factor kappa beta (NF-${\kappa}B$) activity were also decreased in the presence of MZRR. The production of tumor necrosis factor-$\alpha$ (TNF-$\alpha$), the mRNA expression levels of pro-inflammatory cytokines, including TNF-$\alpha$ and IL-$1{\beta}$, were reduced after MZRR administration in a dose dependent-manner. These results suggest that the MZRR extract involved in the inhibition of iNOS and COX-2 via the NF-${\kappa}B$ pathway, revealing a partial molecular basis for anti-inflammatory properties of the MZRR extract.

• Asian Pacific Journal of Cancer Prevention
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• 제14권7호
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• pp.4347-4352
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• 2013

Aim: To investigate the molecular mechanisms underlying triggering of apoptosis by hesperetin using in silico and in vitro methods. Methods: The mechanism of binding of hesperetin with NF-${\kappa}B$ and other apoptotic proteins like BAX, BAD, $BCL_2$ and $BCL_{XL}$ was analysed in silico using Schrodinger suite 2009. In vitro studies were also carried out to evaluate the potency of hesperetin in inducing apoptosis using the human prostate cancer PC-3 cell line. Results: Hesperetin was found to exhibit high-affinity binding resulting from greater intermolecular forces between the ligand and its receptor NF-${\kappa}B$ (-7.48 Glide score). In vitro analysis using MTT assay confirmed that hesperetin reduced cell proliferation ($IC_{50}$ values of 90 and $40{\mu}M$ at 24 and 48h respectively) in PC-3 cells. Hesperetin also downregulated expression of the anti-apoptotic gene $BCL_{XL}$ at both mRNA and protein levels and increased the expression of pro-apoptotic genes like BAD at mRNA level and BAX at mRNA as well as protein levels. Conclusion: The results suggest that hesperetin can induce apoptosis by inhibiting NF-${\kappa}B$.

• 동의생리병리학회지
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• 제26권5호
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• pp.738-744
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• 2012

Gastrodia elata Blume is used for a variety of purposes including treatment of inflammation in the Korean medicine. The present study investigated whether the G. elata extracts have the anti-inflammatory effect on lipopolysaccharide(LPS)-stimulated BV-2 microglia cells. G. elata extracts showed an anti-inflammatory effects in the morphological and nitric oxide(NO) analysis, especially in hexane extract. So we investigated the hexane extract from G. elata in the following experiments. Hexane extract significantly inhibited the secretion of NO with protein level of inducible nitric oxide synthase in LPS-stimulated BV2 microglia cells. Hexane extract also inhibited LPS-stimulated inflammatory responses involving the degradation of cytosolic inhibitory(I)-${\kappa}B{\alpha}$ and the translocation of nuclear factor(NF)-${\kappa}Bp65$ to nucleus in LPS-stimulated BV-2 microglia cells by morphological analysis. Western blot analyse confirmed that I-${\kappa}B{\alpha}$ and NF-${\kappa}Bp65$ showed a similar pattern as morphological analysis. Our results suggest that G. elata extracts, especially hexane extract, may act as a therapeutic agent for inflammatory disease in the central nervous system through a selective regulation of NO production and NF-${\kappa}B$ activation.

• BMB Reports
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• 제42권6호
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• pp.380-386
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• 2009

In neurodegenerative diseases, such as Alzheimer' and Parkinson', microglial cell activation is thought to contribute to CNS injury by producing neurotoxic compounds. Prothrombin and kringle-2 increase levels of NO and the mRNA expression of iNOS, IL-1$\beta$, and TNF-$\alpha$ in microglial cells. In contrast, the human prothrombin kringle-2 derived peptide NSA9 inhibits NO release and the production of pro-inflammatory cytokines such as IL-1$\beta$, TNF-$\alpha$, and IL-6 in LPS-activated EOC2 microglia. In this study, we investigated the anti-inflammatory effects of NSA9 in human prothrombin- and kringle-2-stimulated EOC2 microglia. Treatment with 20-100 ${\mu}M$ of NSA9 attenuated both prothrombin- and kringle-2-induced microglial activation. NO production induced by MAPKs and NF-$\kappa$B was similarly reduced by inhibitors of ERK (PD98059), p38 (SB203580), NF-$\kappa$B (N-acetylcysteine), and NSA9. These results suggest that NSA9 acts independently as an inhibitor of microglial activation and that its effects in EOC2 microglia are not influenced by the presence of kringle-2.